Background
The term septic arthritis (SA) represents an invasion of a joint space by a variety of microorganisms, most commonly bacteria. Various types of viruses, mycobacteria, and fungi also may be involved. Despite timely institution of appropriate treatment, SA continues to produce significant rates of morbidity and mortality. Reactive arthritis represents a sterile inflammatory process that is triggered by a variety of extra-articular infections. [1]
Etiology
Organisms may invade the joint by direct inoculation, by contiguous spread from infected periarticular tissue, or most commonly, via the bloodstream. [2]
The normal joint has several protective components. Healthy synovial cells possess significant phagocytic activity, and synovial fluid normally possesses significant bactericidal activity. Rheumatoid arthritis and systemic lupus erythematosus hamper the defensive functions of synovial fluid and decrease chemotaxis and phagocytic function of polymorphonuclear leukocytes. Patients with deficiencies of the terminal components of complement are susceptible to both Neisserial bacteremia and joint infections.
S aureus is the most common cause of septic arthritis in all age groups. Among those aged 15 to 50 years, N gonorrhea runs a close second, especially among those who are sexually active.
Gonococcal and nongonococcal bacterial/suppurative arthritis
Bacterial SA is commonly described as either gonococcal or nongonococcal. [3, 4, 5, 6, 7, 2] Neisseria gonorrhoeae remains the most common pathogen (75% of cases) among younger sexually active individuals. [8, 9, 10] The increased incidence of S aureus parallels the rise of prosthetic joint implantation, intravenous drug abuse (IVDA), and the use of immunosuppressive agents. This pathogen causes 80% of infected joints affected by rheumatoid arthritis (RA).
Streptococcal species, such as Streptococcus viridans, S pneumoniae, [11, 12] and group B streptococci [13] account for 20% of cases. Aerobic Gram-negative rods are involved in 20-25% of cases. Most of these infections occur among the very young and very old, [14] patients with diabetes, immunosuppressed individuals, and people who use intravenous drugs. [15, 16]
Infection of the cartilaginous joints (sternoclavicular, sacroiliac, and pubic joints) with Pseudomonas aeruginosa or Serratia species occurs almost exclusively among people who abuse intravenous drugs. Individuals with leukemia are susceptible to Aeromonas infections. [17]
Polymicrobial joint infections (5-10% of cases) and infection with anaerobic organisms (5% of cases) are usually a consequence of trauma or abdominal infection. Individuals with multiple pathogens have a higher rate of previous native and prosthetic joint infections. The most common pathogens were coagulase-negative Staphylococcus (CoNS), MSSA, and enterococci. [18]
The pathogen of Lyme disease, Borrelia burgdorferi, commonly produces a septic arthritis picture. [16] Occasionally, the signs and symptoms of the acute infection persist despite successful eradication of this pathogen. This appears to result from ongoing synovial inflammation due to persistent vascular damage, and autoimmune processes that interfere with appropriate tissue healing.
Brucella may cause septic arthritis in areas where cattle are not vaccinated. The organism of Whipple disease, Mycoplasma species, and Ureaplasma species infrequently involve septic joints. [4]
A wide variety of viruses (eg, human immunodeficiency virus [HIV], lymphocytic choriomeningitis virus, hepatitis B virus, rubella virus), mycobacteria, fungi (eg, Histoplasma species, Sporothrix schenckii, Coccidioides immitis, Blastomyces species), and other pathogens produce nonsuppurative joint infections. [17]
Prosthetic joint infections (PJIs)
PJIs are classified according to the onset of symptoms following implantation of the joint.
There are three major categories of PJIs: those that develop within 3 months of implantation; those that appear within 3 to 24 months of implantation; and those that occur later than 24 months. Most cases of early prosthetic joint infection are caused by S aureus. The 3- to 24-month group usually are caused by coagulase-negative S aureus (CoNS) or Gram-negative aerobes, both of which are acquired in the operating room. Late cases of prosthetic joint infection usually are the result of hematogenous spread from a variety of infectious foci. [19, 20] Unusually, they may arise from a dormant infection of periprosthetic tissue.
Early PJI symptoms may occur within 30 days of implantation, but most often symptoms appear more than 30 days after prosthesis implantation.
Symptoms appearing more than 30 days after implantation or lasting more than 30 days may have concomitant sinus tracts. [21]
Pathophysiology
Previously damaged joints, especially those damaged by rheumatoid arthritis, are the most susceptible to infection. The synovial membranes of these joints exhibit neovascularization and increased adhesion factors; both conditions increase the chance of bacteremia, resulting in joint infection. Some microorganisms have properties that promote their tropism to the synovium. S aureus readily binds to articular sialoprotein, fibronectin, collagen, elastin, hyaluronic acid, and prosthetic material via specific tissue adhesion factors (microbial surface components recognizing adhesive matrix molecules [MSCRAMMs]). In adults, the arteriolar anastomosis between the epiphysis and the synovium permits the spread of osteomyelitis into the joint space.
The major consequence of bacterial invasion is damage to articular cartilage. This may be due to the particular organism's pathologic properties, such as the chondrocyte proteases of S aureus, as well as to the host's polymorphonuclear leukocytes response. The cells stimulate synthesis of cytokines and other inflammatory products, resulting in the hydrolysis of essential collagen and proteoglycans. Infection with N gonorrhoeae induces a relatively mild influx of white blood cells (WBCs) into the joint, explaining, in part, the minimal joint destruction observed in cases of infection with this organism relative to destruction associated with S aureus infection.
As the destructive process continues, pannus formation begins, and cartilage erosion occurs at the lateral margins of the joint. Large effusions, which can occur in infections of the hip joint, impair the blood supply and result in aseptic necrosis of bone. These destructive processes are well advanced as early as 3 days into the course of untreated infection.
Viral infections may cause direct invasion (rubella) or production of antigen/antibody complexes. Such immunologic mechanisms occur in infections with hepatitis B, parvovirus B19, and lymphocytic choriomeningitis viruses.
Reactive/postexposure process
Reactive, or postexposure, arthritis is observed more commonly in patients with human lymphocyte antigen B27 (HLA-B27) histocompatibility antigens. Although various infections can cause reactive arthritis, gastrointestinal processes are by far the most common. Gastrointestinal pathogens associated with reactive arthritis include the following [1] :
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Salmonella enteritidis
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Salmonella typhimurium
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Yersinia enterocolitica
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Campylobacter jejuni
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Clostridium difficile
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Shigella sonnei
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Entamoeba histolytica
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Cryptosporidium
Genitourinary infections, especially those due to Chlamydia trachomatis, are the second most common cause of reactive arthritis. The arthritis of Lyme disease usually results from immunologic mechanisms, with a minority of cases due to direct invasion by an organism. A reactive/postexposure process may occur months after the gastrointestinal or genitourinary process has resolved.
COVID-19 infection has been increasingly implicated as a cause of reactive arthritis especially among patients with rheumatoid arthritis. [3, 22]
The Gram-negative coccobacillus Kingella kingae has emerged as a prime etiology of septic arthritis and osteomyelitis in children aged 6-48 months. [23, 24] K kingae is unlikely to be a novel human pathogen; rather, its increased recognition appears to be the result of improved methods of detection. [23]
Gram-negative bacilli are also more common in elderly patients with chronic medical conditions. Pseudomonas aeruginosa and methicillin-resistant S aureus (MRSA) are more prevalent in the infectious arthritis that affects individuals who abuse intravenous (IV) drugs. Salmonella species exhibit a predilection for individuals with systemic lupus erythematosus and those with sickle cell disease. [25]
Prosthetic joint infections
PJIs may be a consequence of local infection, such as superficial surgical site infections/delayed wound healing (60-80% of cases). [21] Twenty to forty percent are due to continuous or transient bacteremias. [4] These may be spontaneous (ie, gingival disease) or secondary to various surgical manipulations. Delayed wound healing is a major factor behind early prosthetic joint infection. This increased risk resolves with the eventual development of a surrounding pseudocapsule, which significantly lessens the infectious risk posed by bloodstream infections.
Recommendations for the use of postoperative prophylactic antibiotics for revisions of total joint arthroplasties have yet to be established. [21]
The biofilm of coagulase-negative S aureus (CoNS) protects the pathogen from the host's defenses, as well as from various antibiotics. Polymethylmethacrylate cement inhibits WBC and complement function.
Overall, the most common organisms of prosthetic joint infections are CoNS (22% of cases) and S aureus (22% of cases). Enteric Gram-negative organisms account for 25% of isolates. [20] Streptococci, including S viridans, enterococci, and the beta-hemolytic streptococci, cause 21% of cases. Anaerobes are isolated from 10% of patients.
Other distinctive host and/or situation-pathogen associations have been described, including Pasteurella multocida, Capnocytophaga species (dog and cat bites), Eikenella corrodens, anaerobes (especially Fusobacterium nucleatum and streptococcal species [human bites]), Aeromonas hydrophila (myelogenous leukemia), P aeruginosa, Serratia species, Candida species (particularly common in persons who abuse intravenous drugs), Mycobacterium marinum (water exposure), S schenckii (gardening), and S pneumoniae (sickle cell anemia).
Unlike their causative role in sickle cell osteomyelitis, Salmonella species are not associated with the septic arthritis of sickle cell anemia. Ten percent to 30% of patients with brucellosis have lumbosacral spine involvement.
Epidemiology
The yearly incidence of bacterial arthritis ranges from 2-5 cases per 100,000 persons in the general population to 28-38 cases per 100,000 persons in patients with rheumatoid arthritis (RA). [26] Approximately 20,000 cases of SA occur in the United States each year (7.8 cases per 100,000 person-years), with a similar incidence occurring in Europe. [3] The incidence of SA-caused disseminated gonococcal infection is 2.8 cases per 100,000 person-years.
Septic arthritis is increasingly common among persons older than 65 years, among immunosuppressed individuals, and among those with various comorbidities, such as diabetes. Fifty-six percent of patients with septic arthritis are male.
By 2030, an estimated 4 million hip and knee arthroplasties will be performed per year in the United States. [4] The incidence of prosthetic joint infection (PJI) among all prosthesis recipients ranges from 2% to 10%. Since postoperative surveillance is limited to the operative hospital, it may result in significant underestimation of the rate of PJIs. [27, 21]
Prognosis
The chief morbidity of septic arthritis is significant dysfunction of the joint, even if treated properly. Fifty percent of adults with septic arthritis have significant sequelae of decreased range of motion or chronic pain after infection. [3] Thirty percent of reactive arthritis cases may become chronic. Complications include dysfunctional joints, osteomyelitis, and sepsis.
Predictors of poor outcome in suppurative arthritis include the following [28] :
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Age older than 60 years
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Infection of the hip or shoulder joints
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Underlying rheumatoid arthritis
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Positive findings on synovial fluid cultures after 7 days of appropriate therapy
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Delay of 7 days or longer in instituting therapy
The mortality rate primarily depends on the causative organism. N gonorrhoeae septic arthritis carries an extremely low mortality rate, whereas that of S aureus can approach 50%. [22]
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A 30-year-old man who was taking steroids presented with a joint effusion and knee pain. Anteroposterior view of the knee demonstrates patchy demineralization of the tibia and femur and joint-space narrowing. This was caused by tuberculoid infection of the joint.
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Septic arthritis. Anteroposterior view of the shoulder demonstrates subchondral erosions and sclerosis in the humeral head. These are relatively late findings of septic arthritis. Periosteal reaction due to coincident osteomyelitis is present adjacent to the surgical neck of the humerus.
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During the progression of infectious arthritis of the hip, this image was obtained early in the disease and shows only concentric joint-space loss.
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Emergency department photograph of infant with septic arthritis of left hip. Child holds hip rigidly in classic position of flexion, abduction, and external rotation, a position that maximizes capsular volume. Patient is relatively comfortable as long as hip joint remains immobile in this position.
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First radiograph in series of 6 (see following images) documenting natural history and complications of inadequately treated septic arthritis of left hip. Child is aged 22 months and had been symptomatic for 1 week before this radiograph was obtained. No bone changes are seen, but left hip is laterally subluxated.
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Second radiograph in series of septic left hip. Three days after presentation and 10 days after onset of symptoms, there is still no change in bone's appearance, but hip joint is further subluxated.
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Third radiograph in series of septic left hip. Three weeks after presentation, left hip is dislocated, and new periosteal bone formation is noted. This last finding is characteristic of associated osteomyelitis of left femur.
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Fourth radiograph in series of septic left hip. Seven weeks after onset, increased opacity is noted in central portion of proximal femoral metaphysis and in proximal femoral epiphysis. Findings are consistent with avascular necrosis of these structures.
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Fifth radiograph in series of septic left hip. Five months after onset, femoral head has been completely resorbed, and femoral shaft has regenerated.
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Sixth radiograph in series of septic left hip. At age 11, or 9 years after onset of infection, hip joint and proximal femoral growth plate are destroyed. Profound limb-length discrepancy is noted, in addition to severely impaired hip function.
Tables
Virus |
Clinical Features of Viral Disease–Associated Arthritis |
Parvovirus B19 |
Occurs in adult women with erythema infectiosum; often an itchy rash |
Hepatitis A |
Muscle aches and rash in 10% of cases |
Hepatitis B |
Onset in the preicteric phase; usually resolves as jaundice develops; chronic arthritis possible in patients with chronic hepatitis B infection |
Hepatitis C |
History similar to hepatitis B joint infection; usually associated with cryoglobulinemia |
Rubella (natural infection and vaccine related) |
Onset is possible before, during, or after the appearance of the rash; usually resolves in a few weeks; may recur and, more commonly, may persist |
Human immunodeficiency virus [HIV] (2 types occur, both with noninflammatory, sterile joint fluid) |
Develops over several days, and severe knee or ankle pain is characteristic; excellent response to nonsteroidal anti-inflammatory agents (NSAIDS) |
Sudden onset of severe pain in the shoulders and elbows, closely resembling an acute gouty attack; opiates often necessary to control pain |
|
Mumps |
Occurs in adult men 2 weeks after the presentation of parotitis |
