Infectious Arthritis

Barry D. Brause

Juliet Aizer

KEY POINTS

Septic arthritis should be diagnosed and appropriately treated with urgency to reduce the risk of permanent loss of joint function.
The microbial etiology of septic arthritis is not predictable; therefore, cultures of synovial fluid and any appropriate extra-articular site should be obtained before starting antibiotic therapy.
Septic arthritis of the hip joint (or any other joint which cannot be drained effectively by percutaneous aspiration) should be treated with surgical drainage as soon as possible.
When evaluating patients with acute polyarticular arthritis, bacteremic or viremic etiologies should be considered.
When evaluating patients with acute synovitis and negative routine bacterial cultures, (a) possible interference with cultures from prior antibiotic therapy, (b) the presence of a fastidious microorganism
[including Borrelia (Lyme disease), anaerobic bacteria, viruses, mycobacteria, and fungi], or (c) a noninfectious etiology, should be considered.
Septic bursitis is associated with pain only on extreme flexion or extreme extension, as opposed to septic arthritis in which pain is elicited even with small degrees of joint motion.

Infectious arthritis (septic arthritis or pyogenic arthritis) represents the invasion of articular synovium by any microorganism. The clinical presentation, course, and prognosis in patients with septic arthritis are determined by the interaction of specific pathogens and host inflammatory responses with the involved synovial tissue, cartilage, and bone. Early recognition of the pathologic process, along with timely, appropriate medical and surgical intervention, can neutralize potentially disabling tissue destruction and can provide a favorable functional outcome.

ETIOPATHOGENESIS

I. ROUTES OF INFECTION

The pathogen arrives at the synovium by one of three routes of infection: hematogenous seeding, contiguous extension from sepsis in adjacent tissue, and direct introduction.

Hematogenous seeding. Infections of the skin and soft tissues, genitourinary tract, respiratory tract, and gastrointestinal tract can spread to the synovial membrane through the bloodstream.
Contiguous spread. Local septic processes in tissue contiguous to the joint, such as cellulitis, infected skin ulcerations, paronychia, infected synovial cysts, and osteomyelitis, can invade synovial membranes by direct extension.
Direct introduction. Microorganisms can be introduced into articular tissue by traumatic injury, arthrocentesis, intra-articular injections, and orthopedic surgery.

II. ESTABLISHMENT OF INFECTION AND JOINT DAMAGE

Invasion of the synovial membrane by microorganisms is the initial event in all pyogenic arthritides involving native (nonprosthetic) articulations. Subsequently, the infection extends into the joint space, where a paucity of phagocytes, antibodies, and complement permits a closed-space infection to be established. As the pathologic process continues, the avascular cartilage is degraded by bacterial and leukocyte enzymes.

The infection progresses at a rate determined by the virulence of the pathogen, the nature and extent of the inflammatory reaction, and the vulnerability of the underlying host tissue. Polymorphonuclear leukocytes, recruited by microbial chemotactic factors, appear to be essential for tissue destruction. Inflamed hypertrophic synovium becomes an aggressive form of granulation tissue (pannus), which expands throughout the entire articulation.
Irreversible loss of joint function is related to the extent of cartilaginous dissolution, which may occur over a very short period, and to the subsequent overgrowth of adjacent osseous tissue in the form of secondary osteoarthritis.

III. MICROBIOLOGY

Stapbylococcus aureus is the most frequent cause of septic arthritis, responsible for up to 65% of infections, particularly in patients with rheumatoid arthritis, diabetes mellitus, or intravenous drug use. Streptococci are isolated in 20% to 30% of cases, often associated with autoimmune diseases, chronic skin infections, and trauma. Gram-negative bacilli are seen in 5% to 20% of patients, including neonates, aging adults, intravenous drug users, and immunocompromised hosts.

Haemophilus influenzae had been the cause of 30% to 60% of septic joints in children younger than 2 years but is now rarely seen because of the magnificent effect of H. influenzae type b vaccination.
Gonococci had earlier accounted for 75% of bacterial joint infections in patients older than 15 years but now accounts for less than 5% as a result of the increased use of safer sex techniques and the marked decrease in the incidence of mucosal gonorrhea.
Coagulase-negative staphylococci are the most common cause of prosthetic joint sepsis, but they do not have a major role in native joint infections.

PREVALENCE

Patients are generally prone to joint infections because of either local factors at their articulations or systemic factors that increase the risk of bacteremia. Therefore, while the annual incidence of septic arthritis is two to five cases/100,000 in the general population, the annual incidence is 28 to 38/100,000 among patients with rheumatoid arthritis.
Predisposing factors, often occurring together, include the following (approximate frequencies given in parentheses):
- Extra-articular infection (25% to 50%).
- Previous damage to joint (27%), resulting from rheumatoid arthritis, osteoarthritis, crystal-induced arthritis, psoriatic arthritis, systemic lupus erythematosus, neuropathic arthropathy, trauma, or surgery.
- Serious underlying chronic illness (19%), usually associated with immunologic defenses, including malignancy, diabetes mellitus, hepatic cirrhosis, renal disease, and parenteral drug abuse.
- Immunosuppressive or corticosteroid therapy (50%).

CLINICAL MANIFESTATIONS

I. ARTICULAR

Synovitis. The acute onset of joint pain is the most characteristic symptom, with increasing severity on flexion, extension, or weight-bearing (joint pain is subacute or chronic in fungal and mycobacterial infection; see specific entities and problems discussed later in this chapter). Articular pain is induced by even minimal degrees of joint motion. Arthralgia produced only by extreme flexion or extreme extension is suggestive of periarticular inflammation, as seen in septic bursitis. Local soft tissue swelling, tenderness, erythema, and warmth accompany a restricted range of motion in the involved articulation. Synovial effusions are present in 90% of cases.
Distribution of the joint involvement. Bacterial arthritis usually affects only one joint; however, polyarticular infection is seen in 10% of patients and frequently reflects bacteremia or viremia. Knees and hips are the most commonly infected joints, but septic arthritis in parenteral drug abusers often affects the sternoclavicular, sacroiliac, or shoulder articulations. Sepsis within the hip joint can be difficult to diagnose because focal symptoms may be minimal and effusions difficult to demonstrate.

II. EXTRA-ARTICULAR

Systemic. Fever is an almost constant feature of pyarthrosis (90% of cases). Systemic sepsis with septic shock can occur with particularly virulent pathogens in vulnerable patients.
Dermatitis-arthritis syndromes. Certain pyarthroses are accompanied by dermatologic manifestations, along with articular involvement. This presentation is most commonly recognized with Neisseria gonorrhoeae and H. influenzae.
- Gonococcal arthritis is often associated with prodromal or concomitant tenosynovitis and erythematous papular, vesiculopustular, or petechial skin rashes characteristic of the disseminated stage of gonococcemia.
- H. influenzae pyarthrosis can be associated with tenosynovitis and erysipeloid, pustular, or petechial rashes. Similar presentations have been described for bacterial arthritis associated with Neisseria meningitidis and Streptobacillus moniliformis (rat bite fever).
- The pathognomonic appearance of erythema chronicum migrans can be essential for the diagnosis of early Borrelia burgdorferi arthritis [Lyme disease (see Chapter 47)].
- Exanthems are important features in the presentation of viral arthritis associated with rubella (infection or vaccination), acute hepatitis B, and parvovirus B19.
Tenosynovitis manifesting as tenderness, erythema, and slight swelling at periarticular tendons can be seen in infectious arthritis due to gonococcus, H. influenzae, atypical mycobacteria, and sporotrichosis.

DIAGNOSTIC INVESTIGATIONS

I. LABORATORY TESTS

The peripheral blood white blood cell (WBC) count is normal in 30% of patients.
All possible foci of infection (sputum, urine, skin lesions, oropharynx, urethra, uterine cervix, and rectum) should be cultured, and at least two blood cultures should be obtained. Specific culture media for gonococci (Thayer-Martin or chocolate agars) should be employed in addition to aerobic and anaerobic media for specimens from mucosal surfaces and skin lesions. Nucleic acid amplification or hybridization tests can be used on endocervical or intraurethral swab specimens as alternatives to gonococcal cultures. In 49% of cases, the same organism is cultured from an extra-articular site and the joint.

II. IMAGING STUDIES

Radiograph of the joint should be obtained to document the extent of previous damage, observe for evidence of osteomyelitis, and provide a baseline for follow-up studies.
- The earliest radiographic sign of joint infection is periarticular soft tissue swelling, with displacement of the adjacent fat pads by synovial edema or an articular effusion during the first week of pyarthrosis. After this period, periarticular osteopenia (subchondral bone rarefaction) develops because of local hyperemia and proinflammatory cytokines in addition to bone atrophy secondary to relative immobility.
- With more fulminant infection, uniform joint space narrowing becomes visible by radiography because of articular cartilage dissolution.
- Subsequently, osseous erosions, induced by pannus, can be seen in subchondral sites or in peripheral areas between the joint capsule insertion and the joint cartilage, where the synovium is in direct contact with bone.
- Eventually, fibrous or bony ankylosis may develop in chronic infections. Radiologic evaluation of the infected joint is helpful but not diagnostic because these anatomic changes are not specific for septic processes.
Radioisotope bone scans may be of value in diagnostic problems involving deep-seated joints such as hip, shoulder, or spine. However, the findings are not specific, and the scan usually has little role in the initial evaluation of acute infectious arthritis.
Ultrasonography can be of value by identifying and monitoring small and deep joint effusions, providing needle guidance for difficult arthrocenteses, and evaluating periarticular tissues.

III. ARTHROCENTESIS

Aspiration of synovial fluid is mandatory for any joint inflammation in which infection is a possibility. Initial aspiration is by closed-needle technique, with a needle large enough (16- to 18-gauge) to permit recovery of thick, purulent material (see Chapter 8). Hip joint sepsis represents an exception to this approach. In this situation, a radiographically guided aspiration may be more appropriate, and assessment should include an orthopedic surgical evaluation because arthroscopic or open surgical drainage may be necessary. Synovial fluid analysis is the basis for initiating therapy and for confirming the specific microbiologic diagnosis (Table 46-1). The following studies are ranked in order of importance; if the size of the synovial fluid sample is small, culture and Gram stain receive priority.

Culture. Optimally, fluid should be inoculated onto media promptly at the bedside, or the sample should be promptly delivered to the laboratory for immediate incubation. Media selection is defined by the clinical picture and should be focused on gram-positive and gram-negative aerobes (blood agar and MacConkey’s agar), Neisseria and H. influenzae (chocolate agar or Thayer-Martin agar), anaerobes (thioglycolate broth), and, if indicated, fungi and mycobacteria.

Cultures of synovial fluid confirm the presence of specific etiologic microorganisms in all bacterial arthritides, except in gonococcal infection, in which only 50% positivity is found, and the diagnosis is then made on the basis of urethral, cervical, pharyngeal, and rectal cultures or on the basis of the presence of tenosynovitis and the characteristic skin lesions of disseminated gonococcemia.

Table 46-1 Synovial Fluid Analysis

	Normal	Inflammation	Bacterial infection
Color	Colorless, pale yellow	Yellow	Yellow
Turbidity	Slight	Turbid	Turbid, purulent
Leukocyte count	<1,000	1,000 to 25,000	10,000 to >100,000
Cell type	Mononuclear	Neutrophils	Neutrophils
Synovial fluid/blood glucose	0.8–1.0	0.5–0.8	<0.5
Gram stain	Negative	Negative	Positive (in 65% of cases)
Culture	Negative	Negative	Positive