Bacteria enter the joint from the bloodstream; from a contiguous site of infection in bone or soft tissue; or by direct inoculation during surgery, injection, animal or human bite, or trauma. In hematogenous infection, bacteria escape from synovial capillaries, which have no limiting basement membrane, and within hours provoke neutrophilic infiltration of the synovium. Neutrophils and bacteria enter the joint space; later, bacteria adhere to articular cartilage. Degradation of cartilage begins within 48 h as a result of increased intraarticular pressure, release of proteases and cytokines from chondrocytes and synovial macrophages, and invasion of the cartilage by bacteria and inflammatory cells. Histologic studies reveal bacteria lining the synovium and cartilage as well as abscesses extending into the synovium, cartilage, and—in severe cases—subchondral bone. Synovial proliferation results in the formation of a pannus over the cartilage, and thrombosis of inflamed synovial vessels develops. Bacterial factors that appear important in the pathogenesis of infective arthritis include various surface-associated adhesins in S. aureus that permit adherence to cartilage and endotoxins that promote chondrocyte-mediated breakdown of cartilage.
TABLE 157-1Differential Diagnosis of Arthritis Syndromes |Favorite Table|Download (.pdf) TABLE 157-1Differential Diagnosis of Arthritis Syndromes
|Acute Monarticular Arthritis ||Chronic Monarticular Arthritis ||Polyarticular Arthritis |
Monarticular rheumatoid arthritis
Nongonococcal bacterial arthritis
Poncet’s disease (tuberculous rheumatism)
Hepatitis B virus
Human T-lymphotropic virus type I
Sickle cell disease flare
Acute rheumatic fever
Inflammatory bowel disease
Systemic lupus erythematosus
Rheumatoid arthritis/Still’s disease
The hematogenous route of infection is the most common route in all age groups, and nearly every bacterial pathogen is capable of causing septic arthritis. In infants, group B streptococci, gram-negative enteric bacilli, and S. aureus are the most common pathogens. Since the advent of the Haemophilus influenzae vaccine, the predominant causes among children <5 years of age have been S. aureus, Streptococcus pyogenes (group A Streptococcus), and (in some centers) Kingella kingae. Among young adults and adolescents, N. gonorrhoeae is the most commonly implicated organism. S. aureus accounts for most nongonococcal isolates in adults of all ages; gram-negative bacilli, pneumococci, and β-hemolytic streptococci—particularly groups A and B but also groups C, G, and F—are involved in up to one-third of cases in older adults, especially those with underlying comorbid illnesses.
Infections after surgical procedures or penetrating injuries are due most often to S. aureus and occasionally to other gram-positive bacteria or gram-negative bacilli. Infections with coagulase-negative staphylococci are unusual except after the implantation of prosthetic joints or arthroscopy. Anaerobic organisms, often in association with aerobic or facultative bacteria, are found after human bites and when decubitus ulcers or intraabdominal abscesses spread into adjacent joints. Polymicrobial infections complicate traumatic injuries with extensive contamination. Bites and scratches from cats and other animals may introduce Pasteurella multocida or Bartonella henselae into joints either directly or hematogenously, and bites from humans may introduce Eikenella corrodens or other components of the oral flora. Penetration of a sharp object through a shoe is associated with Pseudomonas aeruginosa arthritis in the foot.
NONGONOCOCCAL BACTERIAL ARTHRITIS
Although hematogenous infections with virulent organisms such as S. aureus, H. influenzae, and pyogenic streptococci occur in healthy persons, there is an underlying host predisposition in many cases of septic arthritis. Patients with rheumatoid arthritis have the highest incidence of infective arthritis (most often secondary to S. aureus) because of chronically inflamed joints; glucocorticoid therapy; and frequent breakdown of rheumatoid nodules, vasculitic ulcers, and skin overlying deformed joints. Diabetes mellitus, glucocorticoid therapy, hemodialysis, and malignancy all carry an increased risk of infection with S. aureus and gram-negative bacilli. Tumor necrosis factor inhibitors (e.g., etanercept, infliximab), which increasingly are used for the treatment of rheumatoid arthritis, predispose to mycobacterial infections and possibly to other pyogenic bacterial infections and could be associated with septic arthritis in this population. Pneumococcal infections complicate alcoholism, deficiencies of humoral immunity, and hemoglobinopathies. Pneumococci, Salmonella species, and H. influenzae cause septic arthritis in persons infected with HIV. Persons with primary immunoglobulin deficiency are at risk for mycoplasmal arthritis, which results in permanent joint damage if tetracycline and replacement therapy with IV immunoglobulin are not administered promptly. IV drug users acquire staphylococcal and streptococcal infections from their own flora and acquire pseudomonal and other gram-negative infections from drugs and injection paraphernalia.
Some 90% of patients present with involvement of a single joint—most commonly the knee; less frequently the hip; and still less often the shoulder, wrist, or elbow. Small joints of the hands and feet are more likely to be affected after direct inoculation or a bite. Among IV drug users, infections of the spine, sacroiliac joints, and sternoclavicular joints (Fig. 157-1) are more common than infections of the appendicular skeleton. Polyarticular infection is most common among patients with rheumatoid arthritis and may resemble a flare of the underlying disease.
Acute septic arthritis of the sternoclavicular joint. A man in his forties with a history of cirrhosis presented with a new onset of fever and lower neck pain. He had no history of IV drug use or previous catheter placement. Jaundice and a painful swollen area over his left sternoclavicular joint were evident on physical examination. Cultures of blood drawn at admission grew group B Streptococcus. The patient recovered after treatment with IV penicillin. (Courtesy of Francisco M. Marty, MD, Brigham and Women’s Hospital, Boston; with permission.)
The usual presentation consists of moderate to severe pain that is uniform around the joint, effusion, muscle spasm, and decreased range of motion. Fever in the range of 38.3–38.9°C (101–102°F) and sometimes higher is common but may not be present, especially in persons with rheumatoid arthritis, renal or hepatic insufficiency, or conditions requiring immunosuppressive therapy. The inflamed, swollen joint is usually evident on examination except in the case of a deeply situated joint such as the hip, shoulder, or sacroiliac joint. Cellulitis, bursitis, and acute osteomyelitis, which may produce a similar clinical picture, should be distinguished from septic arthritis by their greater range of motion and less-than-circumferential swelling. A focus of extraarticular infection, such as a boil or pneumonia, should be sought. Peripheral-blood leukocytosis with a left shift and elevation of the erythrocyte sedimentation rate or C-reactive protein level are common.
Plain radiographs show evidence of soft-tissue swelling, joint-space widening, and displacement of tissue planes by the distended capsule. Narrowing of the joint space and bony erosions indicate advanced infection and a poor prognosis. Ultrasound is useful for detecting effusions in the hip, and CT or MRI can demonstrate infections of the sacroiliac joint, the sternoclavicular joint, and the spine very well.
Specimens of peripheral blood and synovial fluid should be obtained before antibiotics are administered. Blood cultures are positive in up to 50–70% of S. aureus infections but are less frequently positive in infections due to other organisms. The synovial fluid is turbid, serosanguineous, or frankly purulent. Gram-stained smears confirm the presence of large numbers of neutrophils. Levels of total protein and lactate dehydrogenase in synovial fluid are elevated, and the glucose level is depressed; however, these findings are not specific for infection, and measurement of these levels is not necessary for diagnosis. The synovial fluid should be examined for crystals, because gout and pseudogout can resemble septic arthritis clinically, and infection and crystal-induced disease occasionally occur together. Organisms are seen on synovial fluid smears in nearly three-quarters of infections with S. aureus and streptococci and in 30–50% of infections due to gram-negative and other bacteria. Cultures of synovial fluid are positive in >90% of cases. Inoculation of synovial fluid into bottles containing liquid media for blood cultures increases the yield of a culture, especially if the pathogen is a fastidious organism or the patient is taking an antibiotic. NAA-based assays for bacterial DNA, when available, can be useful for the diagnosis of partially treated or culture-negative bacterial arthritis.
TREATMENT Nongonococcal Bacterial Arthritis
Prompt administration of systemic antibiotics and drainage of the involved joint can prevent destruction of cartilage, postinfectious degenerative arthritis, joint instability, or deformity. Once samples of blood and synovial fluid have been obtained for culture, empirical antibiotics should be given that are directed against the bacteria visualized on smears or the pathogens that are likely in light of the patient’s age and risk factors. Initial therapy should consist of IV administration of bactericidal agents; direct instillation of antibiotics into the joint is not necessary to achieve adequate levels in synovial fluid and tissue. An IV third-generation cephalosporin such as cefotaxime (1 g every 8 h) or ceftriaxone (1–2 g every 24 h) provides adequate empirical coverage for most community-acquired infections in adults when smears show no organisms. IV vancomycin (1 g every 12 h) is used if there are gram-positive cocci on the smear. If methicillin-resistant S. aureus is an unlikely pathogen (e.g., when it is not widespread in the community), either oxacillin or nafcillin (2 g every 4 h) should be given. In addition, an aminoglycoside or third-generation cephalosporin should be given to IV drug users and to other patients in whom P. aeruginosa may be the responsible agent.
Definitive therapy is based on the identity and antibiotic susceptibility of the bacteria isolated in culture. Infections due to staphylococci are treated with oxacillin, nafcillin, or vancomycin for 4 weeks. Pneumococcal and streptococcal infections due to penicillin-susceptible organisms respond to 2 weeks of therapy with penicillin G (2 million units IV every 4 h); infections caused by H. influenzae and by strains of Streptococcus pneumoniae that are resistant to penicillin are treated with cefotaxime or ceftriaxone for 2 weeks. Most enteric gram-negative infections can be cured in 3–4 weeks by a second- or third-generation cephalosporin given IV or by a fluoroquinolone such as levofloxacin (500 mg IV or PO every 24 h). P. aeruginosa infection should be treated for at least 2 weeks with a combination regimen composed of an aminoglycoside plus either an extended-spectrum penicillin such as mezlocillin (3 g IV every 4 h) or an antipseudomonal cephalosporin such as ceftazidime (1 g IV every 8 h). If tolerated, this regimen is continued for an additional 2 weeks; alternatively, a fluoroquinolone such as ciprofloxacin (750 mg PO twice daily) is given by itself or with the penicillin or cephalosporin in place of the aminoglycoside.
Timely drainage of pus and necrotic debris from the infected joint is required for a favorable outcome. Needle aspiration of readily accessible joints such as the knee may be adequate if loculations or particulate matter in the joint does not prevent its thorough decompression. Arthroscopic drainage and lavage may be employed initially or within several days if repeated needle aspiration fails to relieve symptoms, decrease the volume of the effusion and the synovial white cell count, and clear bacteria from smears and cultures. In some cases, arthrotomy is necessary to remove loculations and debride infected synovium, cartilage, or bone. Septic arthritis of the hip is best managed with arthrotomy, particularly in young children, in whom infection threatens the viability of the femoral head. Septic joints do not require immobilization except for pain control before symptoms are alleviated by treatment. Weight bearing should be avoided until signs of inflammation have subsided, but frequent passive motion of the joint is indicated to maintain full mobility. Although addition of glucocorticoids to antibiotic treatment improves the outcome of S. aureus arthritis in experimental animals, no clinical trials have evaluated this approach in humans.
Although its incidence has declined in recent years, gonococcal arthritis (Chap. 181) has accounted for up to 70% of episodes of infectious arthritis in persons <40 years of age in the United States. Arthritis due to N. gonorrhoeae is a consequence of bacteremia arising from gonococcal infection or, more frequently, from asymptomatic gonococcal mucosal colonization of the urethra, cervix, or pharynx. Women are at greatest risk during menses and during pregnancy and overall are two to three times more likely than men to develop disseminated gonococcal infection (DGI) and arthritis. Persons with complement deficiencies, especially of the terminal components, are prone to recurrent episodes of gonococcemia. Strains of gonococci that are most likely to cause DGI include those which produce transparent colonies in culture, have the type IA outer-membrane protein, or are of the AUH-auxotroph type.
Clinical Manifestations and Laboratory Findings
The most common manifestation of DGI is a syndrome of fever, chills, rash, and articular symptoms. Small numbers of papules that progress to hemorrhagic pustules develop on the trunk and the extensor surfaces of the distal extremities. Migratory arthritis and tenosynovitis of the knees, hands, wrists, feet, and ankles are prominent. The cutaneous lesions and articular findings are believed to be the consequence of an immune reaction to circulating gonococci and immune-complex deposition in tissues. Thus, cultures of synovial fluid are consistently negative, and blood cultures are positive in fewer than 45% of patients. Synovial fluid may be difficult to obtain from inflamed joints and usually contains only 10,000–20,000 leukocytes/μL.
True gonococcal septic arthritis is less common than the DGI syndrome and always follows DGI, which is unrecognized in one-third of patients. A single joint such as the hip, knee, ankle, or wrist is usually involved. Synovial fluid, which contains >50,000 leukocytes/μL, can be obtained with ease; the gonococcus is evident only occasionally in Gram-stained smears, and cultures of synovial fluid are positive in fewer than 40% of cases. Blood cultures are almost always negative.
Because it is difficult to isolate gonococci from synovial fluid and blood, specimens for culture should be obtained from potentially infected mucosal sites. NAA-based urine tests also may be positive. Cultures and Gram-stained smears of skin lesions are occasionally positive. All specimens for culture should be plated onto Thayer-Martin agar directly or in special transport media at the bedside and transferred promptly to the microbiology laboratory in an atmosphere of 5% CO2, as generated in a candle jar. NAA-based assays are extremely sensitive in detecting gonococcal DNA in synovial fluid. A dramatic alleviation of symptoms within 12–24 h after the initiation of appropriate antibiotic therapy supports a clinical diagnosis of the DGI syndrome if cultures are negative.
TREATMENT Gonococcal Arthritis
Initial treatment consists of ceftriaxone (1 g IV or IM every 24 h) to cover possible penicillin-resistant organisms. Once local and systemic signs are clearly resolving, the 7-day course of therapy can be completed with an oral fluoroquinolone such as ciprofloxacin (500 mg twice daily) if the organism is known to be susceptible. If penicillin-susceptible organisms are isolated, amoxicillin (500 mg three times daily) may be used. Suppurative arthritis usually responds to needle aspiration of involved joints and 7–14 days of antibiotic treatment. Arthroscopic lavage or arthrotomy is rarely required. Patients with DGI should be treated for Chlamydia trachomatis infection unless this infection is ruled out by appropriate testing.
It is noteworthy that arthritis symptoms similar to those seen in DGI occur in meningococcemia. A dermatitis-arthritis syndrome, purulent monarthritis, and reactive polyarthritis have been described. All respond to treatment with IV penicillin.