47. | Manual of Rheumatology and Outpatient Orthopedic Disorders (LB Spiral Manuals)

Chapter 40 Infectious Arthritis

Manual of Rheumatology and Outpatient Orthopedic Disorders

Chapter 40 Infectious Arthritis

Barry D. Brause

Diagnosis and therapy
Pathogenesis
Routes of infection
Predisposing factors
Clinical presentation
Laboratory studies
Arthrocentesis
Initial treatment
Subsequent treatment
Specific entities and problems

I. Diagnosis and therapy

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 the destruction and provide a favorable functional outcome.

II. Pathogenesis. Invasion of the synovial membrane by microorganisms is the initial event in all pyogenic arthritides involving native (nonprosthetic) articulations. Subsequently, 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 the evolution of 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 and subsequent overgrowth of adjacent osseous tissue.

III. Routes of infection. Microbial arthritis can arise by three routes of infection: hematogenous seeding, extension from sepsis in adjacent tissue, and implantation. Infections of the skin and soft tissues, genitourinary tract, respiratory tract, and gastrointestinal tract can spread to the synovial membrane through the bloodstream. 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. Microorganisms can be introduced into articular tissue through traumatic injury , arthrocentesis, intraarticular injections, and orthopedic surgery.

IV. Predisposing factors include the following (approximate frequencies appear in parentheses):

Extraarticular infection (25% to 50%).
Previous damage to joint resulting from rheumatoid arthritis, degenerative joint disease, crystal-induced arthritis, systemic lupus erythematosus, neuropathic arthropathy, trauma, or surgery (27%).
Serious underlying chronic illness , usually associated with impaired immunologic defenses, including malignancy, diabetes mellitus, hepatic cirrhosis, and parenteral drug abuse (19%).
Immunosuppressive or corticosteroid therapy (50%).

V. Clinical presentation

Articular. The acute onset of joint pain is the most characteristic symptom, with increasing severity on flexion, extension, or weight bearing . 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. Fever is an almost constant feature of pyarthrosis (90% of cases), and systemic sepsis with septic shock can occur with particularly virulent pathogens in vulnerable patients. Synovial effusions are present in 90% of cases. Bacterial arthritis usually affects only one joint; however, polyarticular infection is seen in 10% of patients and frequently reflects concomitant bacteremia. 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, as focal symptoms may be minimal and effusions undemonstrable. Viral arthritides commonly involve multiple joints, particularly in the hands and wrists. Mycobacterial and fungal arthritides generally have a subacute or chronic clinical presentation.
Dermatitis-arthritis syndromes. Certain pyarthroses are accompanied by dermatologic manifestations along with articular involvement. This presentation is most commonly recognized with Neisseria gonorrhoeae and Haemophilus influenzae. Gonococcal arthritis often is 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), which is discussed in Chapter 41. Exanthems are important features in the presentation of viral arthritis associated with rubella and hepatitis B.

VI. Laboratory studies

The peripheral blood white blood cell (WBC) count is normal in 30% of patients.
Culture all possible foci of infection (sputum, urine, skin lesions, oropharynx, urethra, uterine cervix, rectum ), and obtain at least two blood cultures. Specific culture media for gonococci (Thayer-Martin or chocolate agars) should be employed in addition to routine media for specimens from mucosal surfaces and skin lesions. In 49% of cases, the same organism is cultured from an extraarticular site and the joint.
Radiographs 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 as a result of local hyperemia in addition to bone atrophy secondary to relative immobility. With more fulminant infection, uniform joint space narrowing becomes visible by radiography as a consequence 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, as 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.

VII. 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 4 for details of joint aspiration). 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 initiation of therapy and confirmation of the specific microbiologic diagnosis (Table 40-1). The following studies are ranked in order of importance; if the size of the synovial fluid sample is small, culture and Gram's stain receive priority.

Table 40-1. Synovial fluid analysis

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 should be selected for gram-positive and gram-negative aerobes (blood agar and MacConkey agar), N. gonorrhoeae and H. influenzae (chocolate agar or Thayer-Martin agar), anaerobes (thioglycolate broth), and, if indicated, fungi and mycobacteria. Cultures of synovial fluid confirm the specific etiologic microorganism 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 the presence of tenosynovitis and the characteristic skin lesions of disseminated gonococcemia. The age-related incidence of bacterial agents in septic arthritis is seen in Table 40-2.

Table 40-2. Age-related bacteriology of septic arthritis
Gram's stain. Pending the results of cultures, the Gram's stain is the cornerstone of initial antibiotic selection (see section VII. A ).
Cell count and differential. Synovial fluid leukocytosis with predominance of neutrophils is common, but the range of WBC counts is wide (6,800 to 250,000 cells ). The probability of infection increases with higher WBC counts; 40% of patients with bacterial arthritis have synovial fluid WBC counts greater than 100,000, whereas rheumatoid arthritis and crystal-induced arthritis rarely produce these counts.
Note: Gout and pseudogout crystals can be found in the synovial fluids of patients with septic arthritis.
Synovial fluid glucose . In septic joints, this value is usually less than 50% of simultaneous serum levels; however, this relationship holds only for fasting specimens because postprandial blood glucose may not equilibrate promptly with synovial fluid. The synovial fluid glucose level is reduced in only 50% of infected patients, and reductions can be seen in uninfected, inflamed joints in patients with rheumatoid arthritis.
Countercurrent immunoelectrophoresis can rapidly detect antigens from pneumococci, meningococci, and H. influenzae in joint fluid (and urine) and is helpful in establishing the microbiologic diagnosis. Countercurrent immunoelectrophoresis can be diagnostic when prior antibiotic therapy interferes with routine cultures.

VIII. Initial treatment

Antibiotic therapy, empirically based on Gram's stain results, is summarized in Table 40-3. Administration should be initiated promptly and parenterally to ensure reliable serum levels. Most antimicrobial agents achieve effective synovial fluid levels with parenteral dosing; therefore, intraarticular instillation or irrigation is not indicated and may be hazardous. Antibiotics injected directly into the joint space can cause a chemical synovitis and can be absorbed systemically, resulting in potentially toxic serum levels.

Table 40-3. Initial antibiotic therapy for pyogenic arthritis, based on Gram's stain of synovial fluid
Joint immobilization (usually in extension) should be employed only initially when joint pain is incapacitating. As soon as possible, range of motion exercises should be started (without weight bearing), as this technique may enhance nutritional diffusion to cartilage and assist in restoring natural cartilage repair mechanisms inhibited by immobilization. Such exercises should also prevent the development of contractures. Weight bearing should be avoided until joint inflammation has resolved substantially to reduce the risk for damage to articular cartilage.
Analgesics that do not affect fever should be used, such as codeine (30 mg q4h). Antiinflammatory drugs (e.g., aspirin, indomethacin) should not be used initially so that the response to treatment can be assessed. (In addition, these agents are antipyretics.)

IX. Subsequent treatment

General measures. The daily assessment of patient status includes temperature, strength and appetite, change in range of motion in the joint, peripheral blood WBC count, and resolution of any extraarticular foci of infection.
Selection of definitive antibiotic therapy occurs as culture results become available. Antibiotic guidelines for specific pathogens are set forth in Table 40-4.

Table 40-4. Antibiotic therapy based on culture identification of organism
Duration of antibiotic therapy varies with different types of bacterial arthritis. Gonococcal arthritis can be treated with 7 days of parenteral therapy, whereas other bacterial pathogens require 2 to 4 weeks of antibiotic therapy, depending on the microorganism, response to therapy, and condition of the underlying articular tissues. Treatment of infections in prosthetic total joint arthroplasty is discussed in X.H.
Serial joint aspiration. Because septic arthritis is a closed-space infection, drainage procedures are essential to decrease intraarticular pressure and reduce leukocyte enzyme activity. Simple arthrocentesis is commonly adequate to accomplish this aspect of therapy, and serial aspirations are necessary as prompted by reaccumulations of inflammatory effusions, often on a daily basis and occasionally twice daily. The response to therapy can be monitored by serial synovial fluid leukocyte counts. After 5 to 7 days of effective treatment, the joint fluid WBC count should decline by 50% to 75%. Failure to achieve such a reduction should be viewed as an indication of inadequate therapy, and surgical drainage should be considered .
Surgical drainage, often with synovectomy, is indicated in the treatment of hip infections (particularly with Staphylococcus aureus or gram-negative bacilli) because of the mechanical difficulty encountered in percutaneous needle aspiration of this deep articulation. Operative debridement is essential when pyarthrosis is inadequately responsive to arthrocentesis as a consequence of loculation of infection by intraarticular adhesions or underlying joint disease. Arthroscopic techniques have often been employed instead of open arthrotomy for debridement in these situations, especially when the knee is involved. Arthroscopy provides for more complete visualization of the tissue (by magnification and access to posterior compartments), decreases morbidity (lower complication rate), increases joint mobility (earlier postoperative motion because of decreased incision size and associated pain), and is more economical (shorter hospitalization period). The indications for open surgical drainage include the following:
1. Hip infection.
2. Failure of needle aspiration to drain the joint adequately (widely varying WBC counts in repeated aspirates suggest loculated pockets of purulence).
3. Lack of local or systemic response to therapy (e.g., joint fluid cultures remain positive, patient remains febrile after 72 to 96 hours of antibiotic therapy). A low threshold for early exploratory arthrotomy or arthroscopy should be maintained in the compromised host with gram-negative bacillary arthritis.
4. Recrudescent or recurrent infection should prompt consideration of surgical drainage and debridement with histopathologic examination of synovial tissue and cultures for fastidious bacteria, mycobacteria, and fungi if appropriate.

X. Specific entities and problems

Gonococcal arthritis
1. Diagnostic features
  1. Polyarthritis and monarthritis occur in approximately equal proportions at presentation.
  2. Pustulovesicular skin lesions, often with central necrosis, occur in 44% of cases.
  3. Tenosynovitis occurs in 68% of cases.
  4. Positive cultures are obtained from urethra (81%), synovial fluid (60%), blood (24%), pharynx (17%), and rectum (13%).
2. Treatment
  1. Drug therapy (as recommended by the Centers for Disease Control and Prevention)
    1. Ceftriaxone (1 g IM or IV q24h), ceftizoxime (1 g IV q8h), or cefotaxime (1 g IV q8h for 7 days).
    2. For persons allergic to b -lactam drugs, ciprofloxacin (400 mg IV q12h), ofloxacin (400 mg IV q12h), or spectinomycin (2 g IM q12h) should be employed. Quinolones should not be used during pregnancy or in patients likely to have acquired infection in Asia, where resistance has been demonstrated. In certain geographic areas (e.g., Cleveland, Ohio), where strains with decreased susceptibility to quinolones are endemic, quinolones should not be used to treat gonorrhea. Reliable patients with uncomplicated disease in whom all symptoms resolve within 24 to 48 hours may complete therapy (for a total of 7 days of treatment) with either oral cefixime (400 mg twice daily); if not pregnant, with oral ciprofloxacin (500 mg twice daily); or oral ofloxacin (400 mg twice daily).
    3. Indications for hospitalization include inability of patient to follow or tolerate an outpatient regimen, uncertain diagnosis, and presence of a purulent joint effusion.
Tuberculous arthritis
1. Diagnostic features. Presentation is typically a chronic monarthritis or spondylitis. Skeletal tuberculosis is usually a combined osteomyelitis and arthritis, as infective lesions in epiphyseal bone invade the adjacent joint. The chest radiographic findings are often normal, and constitutional symptoms may not be present. The tuberculin skin test result is almost always positive. Synovial fluid analysis reveals an elevated WBC count (usually 10,000 to 20,000/L) with neutrophil predominance (80% of cases). Acid-fast stains of joint effusions are positive in only 27%, and although joint fluid culture is positive in 83%, cultivation requires 4 to 6 weeks of incubation. Synovial biopsy is the procedure of choice for immediate diagnosis; histopathology demonstrates granuloma formation in 95%, caseation in 55%, and the tubercle bacillus in 10% of cases.
2. Treatment consists of isoniazid (300 mg/d) and rifampin (300 mg twice daily) for at least 12 months, with pyrazinamide (25 mg/kg daily; maximum of 2.5 g/d) for the initial 2 months.
Atypical mycobacterial arthritis
1. Diagnostic features. Mycobacterium marinum is the most common cause of atypical tuberculous arthritis. Presentation is usually a subacute or chronic interphalangeal or metacarpophalangeal monarthritis. Symptoms commonly develop several weeks after local traumatic contact with marine life (fish, fishing equipment, fish tanks). Diagnosis is assisted by synovial biopsy revealing granulomas or acid-fast bacilli. Mycobacterial cultures of synovial tissue are diagnostic; however, the microbiology laboratory should be alerted to incubate specimens at 30C for optimal results.
2. Treatment consists of rifampin (300 mg twice daily) and ethambutol (15 mg/kg daily for 6 weeks) or minocycline (100 mg twice daily) for 16 weeks.
Fungal arthritis
1. Diagnostic features. Fungal arthritis usually presents as a chronic monarticular infection, but acute polyarticular disease with or without erythema nodosum can be seen. Diagnosis depends on synovial tissue histopathology and mycotic cultures. Key features of specific types of fungal arthritis follow:
  1. Blastomycosis primarily involves the lungs, with spread to skin and bone; knee, ankle, and elbow are the most commonly affected joints. Synovial fluid culture is positive for the organism in 90% of cases.
  2. Candidiasis causes hematogenous septic arthritis in immunosuppressed hosts . Two- thirds of patients present acutely, 40% have multiple joint involvement, and 65% have evidence of osteomyelitis.
  3. Coccidioidomycosis and histoplasmosis both exhibit an acute, self-limited, hypersensitivity-type polyarthritis with erythema nodosum. Subsequently, a chronic granulomatous infectious synovitis may develop.
  4. Sporotrichosis affects joints rarely by extension of infection from the usual cutaneous and lymphatic or osseous sites of involvement. More frequently, a slowly progressive polyarticular infection develops as a result of hematogenous seeding of the synovium.
2. Treatment of blastomycosis, coccidioidomycosis, histoplasmosis, and sporotrichosis can be successful with oral imidazoles. Candidiasis is treated with IV amphotericin B. Surgical debridement is often necessary to eradicate fungal infection.
Viral arthritis. Rubella virus, hepatitis B virus, and parvovirus are the most common identifiable viral pathogens, although arthritis can be a manifestation of mumps, infectious mononucleosis (Epstein-Barr virus), herpes simplex, or infection with arbovirus, enterovirus, varicella-zoster, or adenovirus.
1. Diagnostic features. Rubella is accompanied by a polyarthritis after appearance of the exanthem and usually resolves within 2 weeks. Polyarthritis also may develop following rubella vaccination. Prodromal hepatitis B is associated with polyarthritis and skin eruptions such as urticaria, maculopapular rashes, petechiae, purpura, and angioneurotic edema. Joint symptoms usually resolve after 1 to 3 weeks coincident with the onset of jaundice. Recurrent arthritis can be seen with chronic active hepatitis or persistent antigenemia.
2. Treatment consists of nonsteroidal antiinflammatory drugs.
Lyme disease is discussed in Chapter 41.
Septic bursitis
1. Diagnostic features. Because of their superficial location, the prepatellar and olecranon bursae are most frequently infected, usually following trauma. Patients present with the acute (2 days) or subacute (12 days) onset of local pain and inflammation, with cellulitis in 75% and regional lymphadenopathy in 25% of cases. Pain is evident on palpation of the bursa and on extreme flexion and extreme extension of the adjacent joint but not on limited motion, as seen in septic arthritis. Infection of the prepatellar or olecranon bursa does not imply involvement of the deeper joints, as there is normally no communication between the two spaces. However, infection of a synovial cyst (e.g., Baker's cyst) does imply the presence of septic arthritis. Bursal fluid analysis reveals abnormalities similar to those of infected joint fluid. The etiologic pathogen is S. aureus in more than 90% of cases.
2. Treatment involves drainage by percutaneous aspiration and antibiotic therapy. Clinically mild infections can be treated with oral antibiotics for 3 to 4 weeks. If such patients worsen or fail to improve within 1 to 2 days, parenteral therapy should be instituted as for more severe infections, with IV treatment for 2 weeks followed by 2 weeks of oral therapy. Serial needle aspirations are necessary for reaccumulations of bursal fluid, and surgical drainage with bursectomy is indicated for persistent infection or chronic inflammation.
Prosthetic joint infection
1. Diagnostic features. Total joint replacement infections can present as acute, fulminant illness with fever, joint pain, local swelling, and erythema when caused by relatively virulent organisms (e.g., S. aureus ). Subacute presentations with gradually progressive joint pain and no fever suggest indolent infection with a relatively avirulent organism (e.g., Staphylococcus epidermidis ). A painful prosthetic joint can be caused by both infection and noninfectious, mechanical loosening. Radiography, bone scan, leukocyte scans, WBC counts, and sedimentation rate are not diagnostic for infection. Therefore, the diagnosis of prosthetic joint infection rests on isolation of the pathogen by arthrocentesis or, occasionally, by exploratory arthrotomy. Staphylococci are the predominant organisms ( S. epidermidis, 22%; S. aureus, 22%), with streptococci in 21%, gram-negative bacilli in 25%, and anaerobes in 10% of cases.
2. Treatment. Eradication of the pathogen in prosthetic joint infection requires removal of the prosthesis. Metallic joint excision followed by 6 weeks of bactericidal parenteral antimicrobial therapy and subsequent reimplantation is successful in 90% to 97% of cases. Prosthetic joint removal with reimplantation in a one-stage procedure employing antibiotic-impregnated cement is successful in 70% to 80% of patients. Occasionally, protracted oral antibiotic therapy is given to suppress prosthetic joint infection when the prosthesis cannot be removed, the pathogen is relatively avirulent, or the prosthesis is not loose.
3. Prevention. Because prosthetic joint infection is a catastrophic event for the patient, prevention is of considerable importance. The hematogenous route is responsible for 20% to 40% of these infections. The use of prophylactic antibiotics in patients with prosthetic joints for events or procedures associated with anticipated bacteremia is controversial at the present time, and the adequacy and cost effectiveness of such measures have not been determined. The American Dental Association and the American Academy of Orthopedic Surgeons have jointly advised that prophylactic antibiotics be given to selected patients undergoing dental procedures associated with significant bleeding (including periodontal scaling). The selected patient populations include persons with inflammatory arthropathies (including rheumatoid arthritis and systemic lupus erythematosis), immunosuppression , diabetes mellitus, malnutrition, hemophilia, previous prosthetic joint infection, and all those who have undergone joint replacement within the past 2 years . Clinical decisions regarding prophylactic antibiotics for expected bacteremias in patients with prosthetic joints should be made on an individual basis. The following schedules are for consideration by physicians who wish to employ prophylactic antibiotics in some settings for certain patients.
  1. Dental procedures (associated with gingival hemorrhage)
    1. Amoxicillin, cephalexin, or cephradine (2 g PO 1 hour before procedure), or
    2. Clindamycin (600 mg PO 1 hour before procedure).
  2. Certain genitourinary and gastrointestinal procedures
    1. Amoxicillin (2 g PO) or vancomycin (1 g IV; 1-hour infusion), plus
    2. Ciprofloxacin (750 mg PO), plus
    3. Metronidazole (500 mg PO 1 hour before procedure; omit metronidazole for urinary tract procedures).

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Stephen A. Paget, M.D., Allan Gibofsky, M.D., J.D. and John F. Beary, III, M.D.
Manual of Rheumatology and Outpatient Orthopedic Disorders

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