Septic arthritis is infection and inflammation of a joint caused by bacterial, fungal, or viral invasion of the synovium. Bacterial septic arthritis involves a single joint in 90% of cases. The knee is the most commonly involved joint, followed by the hip, shoulder, ankle, and wrist. Patients with septic arthritis typi- cally have acute swelling and warmth around the joint, effusion, tenderness to palpation, and extreme pain with minimal range of motion.

Bacteria can reach a joint in four ways: (1) from the blood, that is, via hematogenous seeding during bacteremia;(2) from the out- side environment through direct inoculation of organisms following penetrating trauma, joint aspiration, or surgery;(3) from the localized spread of a nearby soft-tissue infection, such as cellulitis or bursitis; or (4) from spread of a bone infection near the joint (periarticular osteomyelitis).1 Hematogenous seeding is the most common cause of infectious arthritis.

Epidemiology

Septic arthritis is rare in the normal adult population; fewer than 5% of cases of acute arthritis have an infectious cause. Bacterial septic arthritis is more common in infants, the elderly, and patients with impaired immunity. Risk factors include a history of rheumatoid arthritis (RA) or intravenous drug use. Patients with RA are more likely to have multiple joint involvement. Intravenous drug users often have infections in atypical joints, such as the sternoclavicular, sacroiliac, and manubriosternal joints.2,3

Information about patient age, medical history, and risk factors must be obtained because these factors not only identify the potential for infection but also the possible infecting organism. With this information, the physician can initiate empiric antibiotic treatment once the diagnosis is established but before identification of a specific bacterium. Staphylococcus aureus is the most common cause of all joint infections; therefore, empiric antibiotics must cover it, even if there is a specific bacteria associated with a particular demographic. For example, pa- tients with a history of illicit drug use are known to have an increased risk of Pseudomonal infection, but even among these patients staphylococcal infection is common as well. Thus, empiric treatment of infection in these patients must cover that organism as well.

Pathophysiology

Hematogenous septic arthritis occurs when bacteria are able to seed the joint after escaping from the synovial capillaries, which do not have a basement membrane. In normal joints, host defense mechanisms are able to destroy these bacteria; however, when these mechanisms are compromised, the organ- isms can survive and cause infection.

While open trauma to a joint is an obvious risk factor for infection, closed trauma is also a risk factor for reasons that are not entirely clear. Possible explanations include a reactive hyperemia increasing exposure to bacteria, disruption of the local anatomy allowing bacteria easier access to the joint and interfering with defense mechanisms, and formation of a hematoma providing an ideal culture medium for bacterial growth.1

Many bacteria can bind to articular cartilage. S aureus has an increased ability to bind to articular cartilage compared with other bacteria, which may explain why it is the most common pathogen in bacterial septic arthritis.1 Within hours after entering the synovium, bacteria induce a neutrophilic in- filtration of the synovium. Cartilage destruction begins within 48 hours as a result of the release of proteases and cytokines from inflammatory cells and increased intra- articular pressure (Fig. 1).

Figure 1
Photograph of the distal femur of a rabbit that was infected with S aureus but did not receive antibiot- ics. Notice the severe cartilage destruction.
(Reproduced with permission from Goodman SB, Chou LB, Schur- man DJ: Management of pyarthrosis, in Chapman MW (ed): Op- erative Orthopaedics. Philadelphia, PA, JB Lippincott, 1988, pp 847-858.)

While neutrophils are one of the primary host defenses against joint infection, they also are a major cause of joint destruction in septic arthritis.

The cytokine interleukin-1 (IL-1), released by macrophages and tissue monocytes in response to bacteria, plays an important role in the destruction of cartilage. Exposure of the joint surface to IL-1 leads to proteogly- can release, increased secretion of collagenase, release of metalloproteases, activation of latent collagenases, and inhibition of glycosaminoglycan synthesis.1

If the septic process is terminated early, the proteoglycan losses can be reversed and normal function restored. If too much matrix is lost, the chondrocytes are exposed to increased mechanical stress and die, which leads to further matrix loss. The remaining chondrocytes are exposed to more stress and are more apt to die, perpetuating a vicious cycle that can lead to complete joint destruction.4

Bacteriology

In adults, S aureus accounts for 60% of the cases of bacterial septic arthritis.5 Other common organisms include streptococci and gram-negative organisms. Although S aureus is still the most common infectious organism in patients who are intravenous drug users, gram-negative infections, especially Pseudomonal infections, can also be transmitted via intravenous drug use. 2

S aureus is a pathogen that may be found in all children, but when infection occurs, several other organisms need to be considered, based on the age of the patient. In infants from birth to 6 weeks of age, the most likely pathogens are group A and group B streptococci, Streptococcus pneumoniae, and Escherichia coli.6 Neisseria gonorrheae infection acquired via maternal transmission at birth also needs to be considered in this age group.

In children younger than 5 years, an in- creasing number of cases of septic arthritis are caused by Kingella kingae. This organism is thought to colonize the nasopharynx and then spread to the joints via invasion of the bloodstream. Haemophilus influenzae type B (HIB) was a common pathogen in children of this age in the past; however, with the advent of widespread vaccination, HIB infection has become extremely rare. S pneumoniae is also an important organism in this age group.5

In children older than 5 years, S aureus, group A streptococci, and S pneumoniae are the most common pathogens. As children get older, the incidence of staphylococcal infections increases, and the incidence of streptococcal infections decreases.

Disseminated gonococcal infection, classically associated with a syndrome of fever, chills, rash, and migratory arthritis of the large joints, always precedes gonococcal septic arthritis, nor- mally involving a single joint. Although gonococcal septic arthritis is always preceded by systemic gonococcal infection, this stage may go unnoticed in up to 30% of patients.7 Gono- coccal infection is the most common type of infectious arthritis in healthy adults. It generally affects patients younger than 40 years, and women are two to three times more likely to be affected than men.

Clinical Presentation

A typical medical history for septic arthritis would be an 80-year-old female nursing home resident being treated with cortico steroids and methotrexate for RA. She has had increasingly worse knee pain for the past 2 days, with perhaps a history of minor trauma. Upon presentation, her temperature is 100.3°F, and she has a large warm effusion on her knee that is diffusely tender to palpation. She also has extreme pain with minimal range of motion. Although she was able to walk 3 days ago, she now finds weight bear- ing painful. Her skin appears normal, al- though cellulitis, a skin infection, is certainly common in such patients.

Radiographs of the knee joint typically show soft-tissue swelling and periarticular osteopenia consistent with long-term RA. In this setting, there is no particular need for special imaging studies. When hip infection is suspected, ultrasound or MRI may be need- ed because these studies can detect an effu- sion with great sensitivity.

When evaluating a patient for infection, it is helpful to obtain a white blood cell count, erythrocyte sedimentation rate, and C-reactive protein level. The essential laboratory test, how- ever, is the analysis of fluid obtained from joint aspiration. This fluid must be examined microscopically (Gram stain) and then sent to the laboratory for a white blood cell count and culture. Aspirates with more than 50,000 white blood cells per milliliter are thought to represent infection. Some patients with inflammatory arthritis but no infection may have more than 50,000 white blood cells per milliliter, whereas some patients with infection and immune suppression (which limits white cell production) may have less. The best criterion to use depends on the utility (value) of each possible outcome.

The differential diagnosis of septic arthritis depends on the clinical scenario. Conditions to consider include inflammatory arthritis, reactive arthritis (a noninfectious joint inflammation following infection else- where in the body), trauma, superficial infection or abscess near but not in the joint, and collagen vascular disorders.

Treatment and Prevention

The goals of treatment include sterilization of the joint, removal of inflammatory cells and their enzymes, elimination of the destructive synovial pannus, and restoration of function.1 Prompt administration of antibiotics and drain- age of the involved joint can prevent cartilage destruction, minimizing the risk of secondary arthritis, joint instability, deformity, and loss of function. Empiric antibiotics should be started as soon as cultures of the blood and synovial fluid are obtained (ie, before interpretation).

The initial choice of antibiotic should be based on the morphology of organisms visualized on Gram stain, if any, and the likely pathogens based on the patient’s age and risk factors. Antibiotics should be given intravenously to achieve rapid peak serum concentrations. Direct injection of the joint with antibiotics is not advised because it can cause a chemical synovitis.

In order to limit cartilage destruction and decrease intra-articular pressure, early drainage of pus and necrotic material is required. Three methods are available: (1) repeated needle aspiration, often at the bedside; (2) arthroscopic lavage; and (3) arthrotomy (open surgery). For easily accessible joints, such as the knee, repeated needle aspirations can be used; however, patient dis- comfort and the difficulty draining thick collections of pus often make arthroscopy a better choice. For less accessible joints, such as the hip, arthrotomy is the best means for irrigation and débridement. Following arthrotomy, the joint should be closed over suction drainage, which can be removed after several days as the volume of drainage de- creases and the patient’s condition improves. If repeated aspirations are attempted and systemic antibiotics are administered, failure to improve within 48 hours is an indication for surgical drainage.

Postoperatively, the joint should be splint- ed in the functional position with assisted range-of-motion exercises initiated once the inflammatory response has decreased. Pro- longed immobilization should be avoided because it promotes the formation of adhesions, atrophy, and contractures. For joints in the lower extremity, weight bearing should be protected until the inflammation has subsided and range of motion and strength are al- most normal.3

Gonococcal septic arthritis is unique in that surgical drainage may not be needed, even with large effusions. This form of septic arthritis is less destructive and rarely requires surgical decompression. Instead, intravenous ceftriaxone and aspiration may be sufficient. Once there is clear improvement, oral antibiotics can be given for a total of 14 days.

 

Infections of the bones and joints, al- though less common than infections in other parts of the body, are nonetheless significant clinical problems. Read more

The first step of evaluation is to ensure that the back pain is not a harbinger of a serious medical condition. Thus tumor, infection, fracture, and instability should be excluded. A patient’s medical history often provides enough information to determine whether ra- diographs are needed on the first visit. When a patient has had back pain for 6 weeks or longer, imaging studies are usually required.

It is unlikely that an adult younger than 50 years with no history of a prior malignancy has a tumor; the odds are even lower when a patient has no constitutional com- plaints, such as fever, weight loss, or night pain. Infection, likewise, is rare in an other- wise healthy patient. The medical history should include questions about possible immune system compromise (eg, human immunodeficiency virus or use of immune- suppressing drugs, such as steroids) or intravenous drug use. Patients with diabetes mellitus or sickle cell anemia are also prone to bone infections.

Fractures and instabilities are rare unless there is a history of trauma. The exception is a patient with osteoporosis. Osteoporosis may be a typical postmenopausal condition, but it also should be considered as a secondary condition in patients with a history of long-term steroid use, a metabolic abnormality, or recent lactation.

Low back pain may originate from the many discrete anatomic structures in the spine itself, such as the disk, the vertebral body, the spinal nerve roots, the facet joints and their ligaments, and the paraspinal muscles. There also may be a visceral cause for the pain, such as an abdominal aortic aneurysm or kidney infection. The leg pain of sciatica may mimic peripheral nerve diseases or vascular insufficiency. Worrisome findings that should prompt diligent investigation include night pain, pain at rest, fever, unintentional weight loss, acute motor weakness, and unremitting pain of increased severity.

Treatment and Prevention

Back pain resolves spontaneously in most patients; therefore, the principal treatment for most mechanical back pain is to simply “do no harm” as natural recovery takes place. Should diagnostic imaging studies reveal disk degeneration without compression of the spinal nerves, physical therapy with an emphasis on lumbar strengthening and flexibility is indicated. Patients with sciatica and MRI evidence of nerve root compression caused by a disk herniation may benefit from epidural steroid injections to reduce the inflammation around the nerve roots.

Nonsurgical Treatment

The use of anti-inflammatory and mild analgesic medications may aid symptom relief, although some patients will require short courses of narcotic pain relievers. Bed rest is considered inappropriate because it induces atrophy and weakness, although activity modification, such as the avoidance of lift- ing, may be useful in hastening recovery and preventing recurrence. In the acute phase of low back pain, physical therapy modalities, such as heat, ice, and ultrasound may pro- vide relief; however, there is no evidence- based literature to support these treatments.4 Therapy should also include “back school” to educate the patient about proper posture and lifting techniques.

Surgical Treatment

Surgery for sciatica is reserved for patients who do not improve after a few months and are willing to assume the risks of surgery. Diskectomy (surgical removal of the herniated disk material) offers patients the chance for a more rapid initial recovery, especially for radicular symptoms in the legs. However, after a period of years, patients who have had surgery are functionally indistinguishable from patients who have not had surgery.5 Surgical fusion for back pain remains a controversial topic.

Prevention

Preventing back pain is also an area of active investigation. Some believe that a program of spinal and abdominal muscle strengthening exercises may reduce the incidence of low back pain. Furthermore, patients are less de- bilitated by pain if they are fit and exercise regularly. Using education about spinal biomechanics as a preventive strategy has produced mixed results. Decreasing risk factors, such as smoking and obesity, has the force of logic, but there is no evidence that attempting to modulate these risk factors is effective in preventing back pain.

 

 

History and Physical Examination

Patients with back pain can be said to have either mechanical or nonmechanical pain. Read more

Disk Disease

Disk herniation is thought to be a major cause of back pain and sciatica. Intervertebral disks consist of an outer ring and a central core. The outer ring, the anulus fibrosus (translated literally as a “fibrous ring”) can tear as a result of an acute event or attrition. This tear permits the central core of the disk, the nucleus pulposus, to bulge (herniate) from its normal location. The injured disk can compress the nerve roots (Figs. 1 and 2).

Figure 1
Simplified axial view of the lumbar spine at the level of the disk space. A, Normal anatomy. B, The same showing a left-sided, posterolateral herniated disk.

Figure 2
Preoperative axial MRI scan showing a herniated lumbar disk (arrow).
(Reproduced from Greene WE (ed): Essentials of Musculoskel- etal Care, ed 2. Rosemont, IL, American Academy of Ortho- paedic Surgeons, 2001, p 561.)

The nucleus pulposus consists of a gel that contains negatively charged proteins that are able to bind water. Normally, the water will be extruded with load bearing and then imbibed again when the load is lifted, allowing the disk to act as a cushion between adjacent vertebral bodies. The disk therefore acts as a hydraulic shock absorber. When there is a break in the anulus fibrosus, however, some of the nucleus pulposus may escape its central location, resulting in a bulge or herniation. Protruding pieces of nucleus pulposus can then compress a spinal nerve or cause local irritation.

The anulus fibrosus can tear at any point, but the direct anterior and posterior posi- tions are reinforced by the longitudinal ligaments of the spine; thus, the path of least resistance is posterolaterally, toward the neural foramen. A large herniation in the lumbar region can compress the cauda equina, the terminal nerve roots of the spinal cord that have not yet left via their respective foramina. Bilateral sciatic pain or saddle anesthesia (decreased sensation around the perineum) and loss of bowel or bladder control suggests such compression. This presentation demands urgent MRI and possibly emergency surgery.

Degeneration of the disk without herniation can occur after trauma but is also a function of aging. As people age, the disk dehydrates and loses its resilience. Thus, even without overt trauma, it is likely that the disk space of an elderly patient will be radio- graphically abnormal, although not necessarily symptomatic.

Osteoarthritis and Spinal Stenosis

Osteoarthritis is often a continuation of lumbar disk disease. As the disk is no longer able to cushion the joint, abnormal forces and motions are applied to the posterior facet joints and will tend to erode the normal architecture (Fig. 3).

Figure 3
A, Schematic representation of degenerative changes of the spine. Notice the advanced degeneration of the L4-L5 and L5-S1 intervertebral disks, the formation of osteophytes, and the narrowing of the intervertebral foramina (seen here as black space).
(Reproduced from Buckwalter JA, Boden SD, Eyre DR, Mow VC, Weidenbaum M: Intervertebral disk aging, degeneration, and herniation, in Buckwalter JA, Einhorn TA, Simon SR (eds): Orthopaedic Basic Science: Biology and Biomechanics of the Muscu- loskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, p 561.)
B, Lateral radiograph showing marked degenerative changes affecting the disk between L4 and L5. (Reproduced from Greene WE (ed): Essentials of Musculoskeletal Care, ed 2. Rosemont, IL, American Academy of Orthopaedic
Surgeons, 2001, p 557.)

This process is similar to the changes in the knee joint seen after the meniscus is severely damaged or completely removed.

Degenerative disk disease and arthritis can cause spinal stenosis, a condition characterized by narrowing of the canal housing the spinal cord (Fig. 4).

Figure 4
The lumbar spine at the level of the disk space showing spinal stenosis. The shaded region repre- sents bone overgrowth and enlargement of the ligamentum flavum.

Spinal stenosis is commonly caused by overgrowth of the bone osteophytes or by enlargement of the ligamentum flavum. Such overgrowth can put pressure on the neural elements and produce pain in the legs, especially after activity.

Rheumatologic Conditions

The facet joints of the spine are true synovial joints; thus, they are susceptible to any of the inflammatory conditions affecting the synovium. Rheumatoid arthritis can affect the low back, but it is more common in the cervical spine. Ankylosing spondylitis is an inflammatory disorder that affects the low back and pelvis, almost always involving the sacroiliac joint. After a period of years, it may lead to autofusion of vertebral bodies. The characteristic finding of most rheumato- logic conditions is morning stiffness and discomfort that actually improve as the day progresses.

Spondylolysis and Spondylolisthesis

The term spondylolysis refers to a defect of the bone between the superior and inferior articular processes of the vertebra, or pars interarticularis (Fig. 5, A).

Figure 5
A, A lumbar spine segment showing a defect in the right pars interarticularis of the upper vertebra. B, Lateral radiograph of a patient with degenerative spondylolisthesis at L4 on L5 (arrow).
(Reproduced from Greene WE (ed): Essentials of Musculoskeletal Care, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2001, p 564.)

This is a common condition, occurring in 5% of the popula- tion.2 It is also seen in athletes, such as gym- nasts or football linemen, who routinely hyperextend their spines. This bony defect can progress to the point at which the vertebral body above can slip forward onto the one below, causing a condition called spondy- lolisthesis (Fig. 5, B). This progression can be avoided by early detection with bone scan- ning or MRI and activity modification.

Tumors and Infections

Tumors and infections can be described together because both are typically caused by hematogenous (bloodborne) seeding. Tumor masses and epidural abscesses can cause a cauda equina syndrome by direct impingement on the neural elements. They also can cause bone destruction and pathologic fractures (Fig. 6).

Figure 6
SagittalT2-weighted MRI scan of a 35-year-old man in whom spinal osteomyelitis is causing bone de- struction in the vertebral body.
(Reproduced from Orthopaedic In-Training Examination, 2000. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, p 46.)

Almost all spine tumors are either metastatic or blood-cell malignancies. One exception is the osteoid osteoma, a benign tumor found typically in teenagers. This tumor can cause back pain severe enough to warrant excision, but it may resolve without treatment.

Acute low back pain will affect most adults at least once in their lives, yet nearly all will recover spontaneously, often without a precise diagnosis ever being made. Read more

Gout is an inflammatory arthritis associated with elevated serum levels of urate (hyperuricemia). Hyperuricemia results from increased production or impaired excretion of uric acid. Acute inflammatory arthritis results when crystals of uric acid are deposited in joints. The synovium subsequently be- comes hyperemic and swollen, but pannus formation does not occur in acute cases. Neutrophils ingest urate crystals and release me- diators of inflammation. With treatment, these crystals can be removed, and the joint can be returned to normal. Gout has a chronic form in which tophi (chalky deposits of urate surrounded by inflammatory cells) are formed adjacent to the joint. In chronic gout, the synovium reacts to the formation of these tophi by becoming hyperplastic, and pannus is formed that leads to erosion of bone. Tophi typically arise close to the joints, but they may also appear in the soft tissue at some distance from the joint or even in other tis- sues located far from joints (eg, the ear).

Epidemiology

Gout is less common than RA. Unlike RA, it is more prevalent in men by a factor of 9:1. Elevated levels of urate are not synonymous with the presence of gouty arthritis.13 Many people with transiently elevated urate levels will never have arthritis; in those who do, however, the urate levels are often elevated for years before the disease is manifest in the joints.

Pathophysiology

The most common form of gout occurs be- cause of decreased excretion of urate by the kidney. Less common causes of this condition include enzymatic defects or diseases with increased nucleotide production. Diet tends to have a direct effect on gout. Excessive organ meat consumption can lead to in- creased urate levels, and drinking alcohol tends to block the excretion of urate. Taken together, a diet rich in alcohol and organ meats is likely to aggravate gout.

Presentation

Most people with hyperuricemia are asymptomatic. Some will have an acute gouty flare and experience increasing pain over a short number of hours, which typically occurs in only one joint—most often the metatarsophalangeal joint of the great toe. People who experience these types of episodes may re- port recent alcohol consumption or have a known history of asymptomatic hyperuricemia. Objective findings include marked tenderness, erythema, warmth, swelling, and severe limitation of motion. Patients with chronic forms of the disease may also have palpable tophi.14

Diagnostic Imaging

In its initial stage, gout is comparable on radiographs to RA because only soft-tissue swelling is seen; however, as the disease progresses, erosions and ultimately joint destruction may be apparent. The erosions that occur with gout are characteristic and may be easily discerned from those that occur with RA. In patients with gout, new bone formation partially surrounding a tophus creates a characteristic overhanging margin (Fig. 5).

Figure 5
AP view of the foot shows erosions with an over- hanging margin in the distal medial metatarsal of the metatarsophalangeal joint of the great toe. Note that the central joint space is not narrowed or compromised. A lateral view will further delineate the size and location of the erosion.

Laboratory Studies

The measurement of serum urate levels is not particularly helpful in diagnosing gout because gout will not develop in many patients with elevated urate levels. Some patients with active gout may have a normal serum urate level at the time of presentation. Other circumstances may result in hyperuri- cemia, such as renal insufficiency or inges- tion of drugs (eg, thiazide diuretics).

Gout is diagnosed by laboratory testing of the synovial fluid. This fluid will show high levels of white blood cells and, more importantly, characteristic needle-shaped monosodium urate crystals. Because monosodium urate crystals are negatively birefringent (doubly refractive), the precise identification of crystals is made with polarized light. Calcium pyrophosphate may also deposit as crystals in the joint (a condition called pseudogout); these crystals are positively bi- refringent.

Treatment and Prevention

Gouty arthritis can be prevented by reducing elevated urate levels with diet modification or medication. Dietary recommendations include decreased ingestion of purines and decreased alcohol consumption. Drugs that lower serum urate levels include probenecid, which promotes the excretion of urate in the urine, and allopurinol, a xanthine oxidase in- hibitor that decreases the synthesis of uric acid.

Colchicine can be used to treat acute episodes of gout because it blocks neutrophil phagocytosis of urate crystals. NSAIDs, of course, can be used to relieve pain and acute inflammation. Historically, indomethacin has been the agent of choice, but other NSAIDs can be equally effective.15 For patients with chronic renal insufficiency, corti- costeroids are the drug of choice.

Juvenile rheumatoid arthritis (JRA) may present as a systemic disease or as one affect- ing only the joints. Approximately 5% to 10% of children with JRA present with systemic signs, including fever, rash, pericarditis, or hepatosplenomegaly. These patients may have significant laboratory abnormalities, including leukocytosis and anemia. Although this form of disease can occur at any age, most cases are seen in patients younger than 10 years. The degree of joint involvement in this form of JRA can range from mild arthalgias to florid swelling of all joints. Children with this form of the disease appear acutely and gravely ill and may require hospitalization.

Epidemiology

JRA is classified as pauciarticular when it affects four or fewer joints over the first 6 months of the disease and as polyarticular when more than four joints are affected. Both types present with joint swelling over a period of weeks to months. Girls with pauciarticular disease are at high risk for eye involvement (chronic uveitis); boys with this subtype may develop a spondyloarthropathy (spinal arthritis). In children with polyarticular disease, the presence of rheumatoid factor in the blood (found in about 20% of patients) is a risk factor for a more persistent and destructive arthritis.

Pathophysiology

Factors similar to those implicated in RA are thought to affect JRA as well. Specifically, genetic predisposition (HLA-DR4 in seropositive JRA, HLA-DR4 in pauciarticular type I, and HLA-B27 in pauciarticular type II), unknown environmental triggers, and immune reactivity are all thought to be possible causes. The inflammatory synovitis that is the hall- mark of JRA does not differ among subtypes and is generally more vascular than that seen in adults.

Diagnosis

Diagnosis is made by the demonstration of persistent arthritis in one or more joints for a minimum of 6 weeks, the exclusion of other diagnoses and, in the case of systemic disease, the presence of either fever or rash.

Treatment

Once the diagnosis of JRA is established, a therapeutic plan is devised based on the subtype and severity of disease. NSAIDs are standard initial therapy. In systemic disease, second-line agents such as hydroxychloroquine or methotrexate may be added early in the disease course; corticosteroids may be required for pericarditis or disease that is unresponsive to other therapies. Most children with pauciarticular disease will respond to an appropriate NSAID. Intra-articular corticosteroids may be needed, and occasion- ally second-line agents such as sulfasalazine are added. Patients with persistent, severe systemic or polyarticular disease who do not adequately respond to methotrexate therapy are candidates for treatment with anti-TNF drugs. Low-dose, short-term corticosteroid therapy may be needed. Long-term cortico- steroid use in children is avoided because steroids may cause growth retardation, iatrogenic Cushing’s disease, osteoporosis, fractures, and hypertension.

In addition to drug therapy, children with JRA must be carefully monitored for growth abnormalities, nutritional problems, and school and social dysfunction. Psychological and emotional health may be difficult to maintain in the presence of chronic disease. Therapeutic exercise programs can maximize joint motion and minimize muscle atrophy.

Adult Rheumatoid Arthritis

heumatoid arthritis (RA) is a chronic inflammatory disease that is probably triggered by an antigen and presents

as an inflammatory reaction against the synovium in the joint (Fig. 1).

Figure 1
Pathogenesis of RA is complex, involving immune processes lead by T cells, cytokine-driven events (responsible for most of the erosive events), and fibroblast-like synoviocyte transformation, resulting in pan- nus formation, hypercellularity, and hyperplasia.
(Reproduced from Recklies AD, Poole AR, Banerjee S, et al: Pathophysiologic aspects of inflammation in diarthrodial joints, in Buckwalter JA, Einhorn TA, Simon SR (eds): Ortho- paedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 489-530.)

This immune process leads to a proliferative synovitis (pannus formation), which proceeds to destroy the joint. Clinically, RA follows a course of waxing and waning, but it results in progressive disability over time. Patients with RA may be disabled from the disease beyond its effect in the joints. For example, RA can cause systemic manifestations, such as fatigue, weight loss, or anemia. In addition, RA is often treat- ed with potent drugs; thus, patients are potentially exposed to complications from medications.

The initial effects of RA in the joint are manifest as stiffness, and the disease may progress to complete destruction of the articular surfaces. The damage is inflicted by the proliferative synovium itself, which tends to physically invade the joint space, as well as by enzymes that the synovium and reactive white blood cells release. RA also affects the ligaments of the joint; therefore, instability and deformity are characteristic (Fig. 2)

Figure 2
Advanced RA. Note that the fingers are deviated toward the ulnar side of the hand because synovitis destroys the tendon sheath. A, Clinical appearance. B, Radiographic appearance.
(Reproduced from Greene WB: Essentials of Musculoskeletal Care, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2001, p 213.

.

RA represents the intersection between musculoskeletal medicine and the basic sci- ence of immunology and inflammation. It is therefore a rich and, at times, recondite subject. This chapter perforce is but an overview.

Epidemiology

RA affects approximately 1% of the population in the United States. Approximately two of every three patients with RA are female.1 RA typically occurs in patients between the ages of 40 and 60 years, although there is a juvenile form that can be found in those younger than 16 years. There appears to be a genetic susceptibility to this condition, as a monozygotic twin of a patient with RA is more likely to have the condition than a dizygotic twin. However, genes are not the only factor affecting susceptibility because even a mono- zygotic twin has only approximately a 15% chance of having RA when the twin has it.

Pathophysiology

The exact etiology of RA is not known. It is thought that exposure to an antigen in a genetically susceptible host leads to an antibody production directed against the synovium. In this model, the antigen activates T cells, which produce cytokines. These mediators stimulate antibody production by B cells.4-6 Among these antibodies is the classic rheumatoid factor that binds to IgG. These antibodies are then deposited as immune complexes in the synovium and in cartilage. Activation of other white blood cells promotes a chronic inflammatory state (Fig. 3).

Figure 3
Cytokines found in the joint initiate and perpetuate many different inflam- matory processes. TNF -α is thought to control many of the processes attributed to inflammatory cells in the joint fluid, and IL-1 is thought to act within the articular cartilage itself. The role of IL -15 in this hierarchy is currently hypothetical, but existing data suggest that IL-15 may act to initiate the T-cell driven autoimmune process.
(Reproduced from Recklies AD, Poole AR, Banerjee S, et al: Pathophysiologic aspects of inflammation in diarthrodial joints, in Buckwalter JA, Einhorn TA, Simon SR (eds): Ortho- paedic Basic Science: Biology and Biomechanics of the Musculoskeletal System, ed 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2000, pp 489-530.)

Synovial proliferation follows this immune activation, a process called pannus formation. The pannus is hyperplastic synovium with fibroblasts, blood vessels, macrophages, and lymphocytes. The synovial cavity of the joint becomes filled with fluid (an inflammatory effusion). The pannus itself, synovial fluid inflammatory cells, and bone-based osteoclasts attack cartilage and bone, resulting in joint destruction.7-9 This destruction produces two characteristic radiographic features of RA: marginal ero- sions and symmetric narrowing of the joint space medially and laterally. Osteoarthritis, by contrast, tends to produce asymmetric joint space narrowing, beginning on the point of maximal force bearing or previous trauma.

Extra-articular manifestations of RA can occur, the most common of which is a sub- cutaneous nodule found near the joint. Rheumatoid nodules contain granulation tissue and inflammatory white blood cells. The synovitis of RA often extends to the tendon sheath as well, leading to its destruction. In patients with RA of the hand, loss of the tendon sheath causes ulnar deviation of the fingers because the tendons no longer remain tethered to the digit. In some patients with RA, inflammation in the heart, lung, or blood vessels may also occur.

The destruction of the joint in patients with RA is modulated by various factors. These include various cytokines as well as specific matrix-destroying enzymes.10 These factors are elaborated from the synovial macrophages and invading T cells. The activation of these cells is thought to be responsi- ble for the extra-articular manifestations of the disease.

Presentation

The presentation of RA depends on the stage of the disease. Moreover, expression of the disease varies not only from individual to individual but also within the same individual over time. RA often begins as an acute period of non- specific complaints, such as malaise and joint pain. Characteristically, patients have diffuse joint tenderness and swelling, accompanied by morning stiffness lasting for at least 1 hour. The commonly accepted criterion is that these findings must be present for at least 6 weeks to make a diagnosis of RA (transient inflammation may have other, more benign causes). Patients with RA will demonstrate tender, warm, and swollen joints and have pain with motion. When the disease is long-standing, there will be characteristic objective findings, such as ulnar deviation of the fingers and radial deviation of the wrist caused by erosion of the extensor tendon sheath. Flexion or extension deformities of the fingers are also common.

Diagnostic Imaging

Imaging for RA in its early stages may not be diagnostic. Because RA begins by attacking soft tissue before bone, in its early stages, signs are not readily apparent on plain radiographs. As the disease progresses, osteopenia caused by increased blood flow and osteoclast activity can be detected. Marginal erosions of the bone are seen as the pannus begins to destroy bone. As the disease progresses, symmetric joint space narrowing occurs, culminating in total destruction of the articular surface (Fig. 4).

Figure 4
AP (A) and lateral (B) radiographs of the hip of a 56-year-old man with RA show moderate diffuse periarticular osteopenia, loss of joint space, and extensive acetabular cyst formation (arrow).
(Reproduced from Lachiewicz PF: Rheumatoid arthritis of the hip. J Am Acad Orthop Surg 1997;5:332-338.)

RA can cause instability of the cervical spine when tenosynovitis near the C1-C2 junction destroys the transverse ligament holding the odontoid.11,12 A cervical spine radiograph is therefore mandatory prior to elective endotracheal intubation of patients with RA.

Laboratory Studies

Laboratory studies may be helpful in the diagnosis of RA, but RA is not conclusively diagnosed on the basis of any single laboratory test result. The most useful laboratory test is probably the aspiration and analysis of the joint fluid, which is performed not so much to make the diagnosis of RA, but to exclude two other conditions that may mimic it: infectious arthritis and gout. When infectious arthritis or gout is present, bacteria or urate crystals usually are apparent on analysis of aspirated joint fluid. The fluid in RA is typically characterized by increased neutrophil concentration but only to moderate lev- els; cell counts are usually in the 5,000 to 50,000 range. A complete blood cell count of patients with RA may show an elevated white blood cell count in the peripheral circulation and anemia as well. Two useful tests for evaluating systemic inflammation involve deter- mining the serum C-reactive protein concentration and the erythrocyte sedimentation rate.

Circulating rheumatoid factor also can be measured. The sensitivity of rheumatic factor for the diagnosis of RA is approximately 80%; therefore, it is a poor screening test. However, its relatively high specificity (approximately 95%) allows it to be used as a confirmatory test. Serial monitoring of rheumatoid factor levels does not offer valuable clinical information. In general, patients with RA who do not have circulating rheumatoid factor have a more benign course.

A number of clinical features have been associated with an unfavorable prognosis. These include persistent polyarticular synovitis for more than 2 years, the presence of articular erosions, and the presence of extra-articular manifestations. Extra-articular manifestations may be general and include fatigue, low-grade fever, weight loss, or anorexia; or they may be organ-specific and include subcutaneous nodules, interstitial lung disease, pleural effusions, or neuropathy. The presence of extra-articular manifestations usually mandates aggressive antirheumatic therapy.

Treatment and Prevention

There is no known prevention for RA. Nonetheless, aggressive treatment of early forms of the disease can be viewed as a preventive measure in that damage is prevented—that is, the disease process is arrested before it is able to destroy joints.

The management of RA is centered on drug therapies, although patient education, supportive counseling, and exercise are also essential to attain a good outcome. The phar- macologic therapy of RA is directed to relieve joint pain, limit inflammation, and retard joint destruction. Because the inflammation of RA is mediated by cytokines, drugs that block them are most effective. Nonsteroidal anti-inflammatory drugs (NSAIDs) are nonspecific inhibitors of prostaglandin synthesis. Accordingly, they can control joint pain, but they do not retard joint destruction. Corticosteroids are also used to limit inflammation. Both NSAIDs and corticosteroids ex- pose the patient to the risk of complications. NSAIDs increase the risk of gastrointestinal bleeding and renal dysfunction, whereas the long-term use of corticosteroids frequently produces osteoporosis and other serious complications.

Another category of drugs used to treat RA is called disease-modifying antirheumatic drugs (DMARDs). The goal of using DMARDs is to prevent joint destruction. The most fre- quently used DMARD is methotrexate, which can slow the progression of joint destruction in patients with RA. Methotrexate is a known inhibitor of folate metabolism; however, its precise effect on RA is not clear. Other DMARDs include immunosuppressive medications, such as sulfasalazine or cyclosporine, and newer biologic agents directed at inhibiting the actions of tumor necrosis factor (TNF)-α or interleukin-1 (IL-1).

The surgical treatment of patients with RA includes joint arthroplasty for damaged joints, fusion of unstable joints, and tenosyn ovectomy to prevent tendon rupture.

Differential Diagnosis

RA can be confused with other forms of inflammatory arthritis, such as systemic lupus erythematosus and viral arthritis. It may also be confused with septic arthritis and gout because both are inflammatory conditions that produce fluid in the joints and pain. Appropriate laboratory tests, however, should be able to differentiate these conditions from RA. RA can also be confused with seronegative spondyloarthropathies, inflammatory joint diseases that occur in the absence of rheumatoid factor (hence, the term serone- gative). These conditions affect the sacroiliac joint and frequently the spine and include ankylosing spondylitis and psoriatic arthritis. Although clinically important and scien- tifically interesting, an in-depth discussion of seronegative spondyloarthropathies is beyond the scope of this book.

1. Brandt KD: The role of analgesics in the manage- ment of osteoarthritis pain. Am J Ther 2000;7:75-90.

2. Brandt KD: (ed): Diagnosis and Nonsurgical Management of Osteoarthritis, ed 2. Caddo, OK, ProfessionaCommunications, Inc, 2000.

  1. Shamoon M, Hochberg MC: The role of acetaminophen in the management of patients with osteoarthritis. Am J Med 2001;110(suppl 3A): 46S-49S.
  2. Katz JN: Preferences, quality, and the (under) utili- zation of total joint arthroplasty. Med Care 2001;39:203-205.
  3. Pavelka K: Osteonecrosis. Baillieres Best Pract Res Clin Rheumatol 2000;14:399-414.

6. Mirzai R, Chang C, Greenspan A, et al: Avascular necrosis. Compr Ther 1998;24:251-255.

7. Klippel JH, Weyand CM, Wortmann RL: (eds): Primer on the Rheumatic Diseases, ed 11. Atlanta, GA, Arthritis Foundation, 1997, pp 216-221, 322- 324, 378-381.

8. Klenerman L: The Charcot joint in diabetes. Diabet Med 1996;13(suppl 1):S52-S54.

9. O’Connor BL, Brandt KD: Neurogenic factors in the etiopathogenesis of osteoarthritis. Rheum Dis Clin North Am 1993;19:581-605.

10. Guyton GP, Saltzman CL: The diabetic foot: Basic mechanisms of disease. J Bone Joint Surg Am 2001;83:1084-1096.

11. Wilson M: Charcot foot osteoarthropathy in diabe- tes mellitus. Mil Med 1991;156:563-569.