Septic arthritis has long been considered an orthopedic emergency. Historically, Neisseria gonorrhoeae and Staphylococcus aureus have been the most common causes of septic arthritis worldwide but in the modern era of biological therapy and extensive use of prosthetic joint replacements, the spectrum of microbiological causes of septic arthritis has widened considerably. There are also new approaches to diagnosis but therapy remains a challenge, with a need for careful consideration of a combined medical and surgical approach in most cases.
Septic arthritis is a major complication in both immunocompetent and immunocompromised hosts. It has long been viewed as an orthopedic emergency as it can lead to significant morbidity and even mortality. In addition, septic arthritis features prominently among the differential diagnoses of arthritis syndromes. Septic arthritis is sometimes difficult to diagnose, and depending on the etiology, it may present as acute monoarticular arthritis, chronic monoarticular arthritis, polyarticular arthritis, or prosthetic joint infection.
Although all types of septic arthritis are infectious, not all infectious arthritis would be classified as septic arthritis in most contemporary classifications. For example, most viral arthritides and reactive arthritides are generally not classified as septic arthritis, although associated with infectious agents.
Viruses such as parvovirus and rubella are well-known causes of either monoarticular or polyarticular arthritis. The recently recognized alphaviruses – most commonly Ross River virus and now chikungunya – characteristically affect the large- and medium-sized joints and have well-defined geographic distributions. Chikungunya can cause chronic arthritis, with symptoms persisting for up to a year . Chikungunya is a mosquito-borne virus spread by the Aedes mosquito and has been increasingly recognized in the western part of the world, including southern United States. In cases of either alphavirus infections or infections due to other viruses, viruses are rarely isolated from joint fluid. Viral arthritis mainly involves the synovium and is usually self-limiting, with the articular cartilage relatively spared . Arthritis can also result from the deposition of immune complexes and complement components in the synovial membrane, for example, in hepatitis B and C infections.
Reactive arthritis is characteristically an oligoarthritis that arises following an acute infection – most commonly of the genitourinary or gastrointestinal tract – and associated with cutaneous changes and fever. Examples include rheumatic fever, Reiter’s syndrome, and the arthritis that occurs after gastrointestinal tract infections with Shigella spp., Salmonella spp., Campylobacter jejuni , or Yersinia enterocolitica . There are associations with HLA-B27, and a detailed description of reactive arthritis is beyond the scope of this chapter. Lyme arthritis is also, not strictly speaking, a form of septic arthritis, although it is caused by an infectious agent. For the remainder of this review, we will focus on the traditional understanding of septic arthritis caused by bacteria, mycobacteria, or fungi.
Route of infection
The hematogenous route of infection is the most common route in all age groups. Infections can also occur after penetrating injuries (including animal bites and scratches, and human bites) and from the local spread of infection but at a lower frequency compared with hematogenous spread .
Route of infection
The hematogenous route of infection is the most common route in all age groups. Infections can also occur after penetrating injuries (including animal bites and scratches, and human bites) and from the local spread of infection but at a lower frequency compared with hematogenous spread .
Predisposing factors for septic arthritis were identified in a 2007 systematic review: age greater than 80 years, diabetes mellitus, rheumatoid arthritis, prosthetic joint, recent joint surgery, skin infection and cutaneous ulcers, intravenous drug abuse and alcoholism, and previous intra-articular corticosteroid administration . Elderly individuals are more likely to have underlying osteoarthritis as well as complications of treatment including joint injections or joint replacements, which could predispose them to septic arthritis. In particular, bacteremia is more likely to localize in a joint with preexisting arthritis, particularly if associated with synovitis . Patients with rheumatoid arthritis often have other risk factors including prior intra-articular corticosteroid injections and maintenance immunosuppressive agents, including anti-tumor necrosis factor (TNF) therapy.
Skin infections and cutaneous ulcers can lead to contiguous septic arthritis, especially in patients with neuropathy and diabetes mellitus. Patients with diabetes mellitus are also immunocompromised for a variety of reasons and have microvascular and macrovascular diseases, which can lead to soft tissue infections and contiguous bone and joint infections .
Prosthetic joints are at risk of infection because of the underlying osteoarticular disease and, in particular, because of the presence of a foreign body and the development of a biofilm . Intravenous drug users are at increased risk of hematogenously derived septic arthritis because of the risk of bloodstream infections and endocarditis.
Hematogenous septic arthritis is usually monomicrobial. Polymicrobial infections are less common but can be seen in penetrating injuries or during contiguous spread from adjacent soft tissue infections and rarely caused by polymicrobial bloodstream infections.
In the modern era, the most common causative organism for monomicrobial septic arthritis is Staphylococcus aureus . In adults of all age groups with non-gonococcal septic arthritis, S. aureus is the most common causative organism . This is mostly hematogenous as S. aureus is the most common cause of bloodstream infections worldwide, although S. aureus can also cause septic arthritis from contiguous extension from an adjacent soft tissue infection. S. aureus bloodstream infections occur often after minor trauma or in health-care settings in association with a central venous catheter or peripheral intravenous device . S. aureus possesses a number of virulence factors, which enable the bacterium to enter the joint space and evade normal host defenses to cause symptomatic infection. These include bone sialoprotein-binding protein, collagen-binding protein, clumping factors A and B, and protein A, all of which share similar mechanisms of action – adhesion to extracellular matrix – leading to septic arthritis and osteomyelitis .
An important subset of S. aureus septic arthritis is septic arthritis caused by methicillin-resistant S . aureus (MRSA). First described several decades ago , septic arthritis caused by MRSA was originally described in hospitalized patients due to seeding of either native or prosthetic joints by MRSA in the setting of nosocomial bloodstream infections. In some populations of intravenous drug abusers, MRSA is the most common pathogen causing septic arthritis . In recent years, community-associated MRSA (CA-MRSA) is being increasingly reported from different parts of the world, including USA , Europe , Taiwan , and Australia . A systematic review by Vardakas et al. found that CA-MRSA bone and joint infections mainly affect patients younger than 2 years of age and African Americans – the reasons for this are not clear and it may be related to access to care or atypical presentations of bone and joint infections in very young children . For patients with septic arthritis of the hip or knee, if a patient were from a health-service-related environment, this was associated with an infection by MRSA more than that of a methicillin-sensitive S. aureus .
In the pre-antibiotic era, the most common cause of septic arthritis was gonococcal septic arthritis caused by Neisseria gonorrhoeae . Among young sexually active adults, N. gonorrhoeae remains the most common causative organism. N. gonorrhoeae septic arthritis is suspected when a patient is young and sexually active; when there is associated tenosynovitis or vesicular pustules on the skin; or when the patient has a late complement deficiency. Although, historically, N. gonorrhoeae primarily affects the knee , there have been reports of N. gonorrhoeae infections of the axial skeleton as well .
Streptococci are the second most common causes of non-gonococcal septic arthritis in the modern era. These infections could be hematogenous – in cases of streptococcal bloodstream infections, which are often associated with gastrointestinal pathologies, especially Streptococcus bovis (now renamed Streptococcus gallolyticus , spp. gallolyticus ) , including group G and group C streptococci . Group A streptococcal infections include the highly fatal streptococcal toxic shock syndrome and necrotizing fasciitis .
In Asia, serious infections are often caused by hypervirulent strains of Klebsiella pneumoniae , and these are often capsular serotypes K1 and K2 and are community acquired . These include bloodstream infections, which lead to septic arthritis . Intriguingly, there have been reports associating strains of Klebsiella spp. with HLA-B27-associated arthritides , via the mechanism of molecular mimicry. Several other gram-negative infections that cause bloodstream infections have also been associated with septic arthritis including primarily Enterobacteriaceae. Among the Enterobacteriaceae, Escherichia coli is the most commonly implicated organism causing bacteremic septic arthritis . Other Enterobacteriaceae that have been reported to cause septic arthritis include Enterobacter spp., Proteus spp., Salmonella spp., Morganella morganii , Citrobacter spp., and Serratias pp .
Many of these infections caused by gram-negative bacilli are health-care associated and are caused by seeding of both native and prosthetic joints from health-care-associated bloodstream infections. Among the non-fermenting gram-negative bacilli, Pseudomonas aeruginosa has been implicated as a cause of septic arthritis after invasive procedures, for example, after prostate resection , and urologic surgery , and as a cause of septic arthritis of the knee after anterior cruciate ligament surgery and intra-articular injection of the knee . Burkholderia cepacia and Acinetobacter baumannii have also been implicated as causative pathogens, especially following procedures.
In endemic countries, Burkholderia pseudomallei is an important cause of community-acquired septic arthritis in native joints. This is a soil organism that is geographically concentrated in Southeast Asia and northern Australia. It can cause an acute septic picture with rapid development of septic shock in individuals without any underlying immune deficiency, although it tends to occur more commonly in patients with diabetes mellitus , renal disease , or alcoholism . Such patients are often bacteremic and can seed their joints with B. pseudomallei . It was found that the most important risk factor identified in patients with septic arthritis caused by B. pseudomallei was diabetes mellitus . Chronic melioidosis can present years after leaving an endemic area – this was described in US military personnel years after leaving the Vietnam War and many individuals have presented years later with bone and joint infections caused by B. pseudomallei , which were not easy to diagnose as the pathogen is not well known outside the tropics .
Other gram-negative organisms and anaerobic bacteria can cause polymicrobial septic arthritis complicating soft tissue infections, most commonly in neuropathic individuals with pressure ulcers, due to spinal cord injury . Patients with ischemic limbs or chronic ulcers due to chronic venous insufficiency or arterial insufficiency may also have polymicrobial septic arthritis of the ankle or knee caused by gram-negative and anaerobic organisms in addition to staphylococci and streptococci . While making a microbiological diagnosis of a septic arthritis in a patient with a chronic ulcer, for example, of the ankle adjacent to a malleolar ulcer, it is critical not to depend on superficial swabs as these superficial swabs often only provide information on the organisms that are colonizing the surface of the ulcer. Samples should be obtained aseptically by going through “clean” skin. Many of these infections are indeed due to S. aureus , although gram-negative bacteria and anaerobic organisms such as Bacteroides fragilis and Prevotella spp. are important pathogens in diabetic foot infections .
In the pediatric age group, the most common organisms after S. aureus are Streptococcus pneumoniae , group A streptococcus, Kingella kingae , and Salmonella spp . Haemophilus influenzae type b is a major cause of septic arthritis in unimmunized populations. In neonates, the most common causes are S. aureus and group B streptococcus . Enteric gram-negative bacilli such as Klebsiella spp., E. coli , Enterobacter spp., non-typhoidal Salmonella spp., P. aeruginosa , and Proteus spp. are rare causes of septic arthritis in neonates in Western countries, but there are increasing reports in developing countries often due to nosocomial infections or unsafe water or injection practices. Other rare causes in neonates include coagulase-negative Staphylococcus , S. pneumoniae , group A streptococcus, Candida spp. , and anaerobes .
Individuals who are immunosuppressed can be infected with rarer organisms. Although staphylococci and streptococci are still the most common causes of septic arthritis in immunocompromised individuals, rarer opportunistic pathogens have been described. Among those reported include various Legionella species (e.g., Legionella pneumophila , Legionella bozemanae , Legionella dumoffii ), Sphingomonas paucimobilis , and B. cepacia complex . Bordetella holmesii , a well-described pathogen in asplenic and immunocompromised patients, has been reported rarely in immunocompetent patients . Although Cellulosimicrobium cellulans usually causes infection in immunosuppressed patients, there has been a case report of this organism causing septic arthritis after a penetrating injury in an immunocompetent patient .
Mycoplasma hominis , which is a commensal in the genitourinary tract of both males and females, usually causes infections such as pyelonephritis, pelvic inflammatory diseases, and postpartum sepsis. Uncommonly, it has also been reported as a cause of septic arthritis in prosthetic joints as well as in immunocompromised hosts . Steuer et al. reported a case wherein M. hominis septic arthritis was the presenting symptom for common variable immunodeficiency .
Patients who are neutropenic because of either underlying diseases, such as aplastic anemia, or chemotherapy-induced neutropenia are at risk of bacterial infections, in particular gram-negative bacterial infections. These often arise endogenously from translocation of enteric gram-negative bacilli that colonize the gastrointestinal tract. P. aeruginosa remains an important organism in this category. Neutropenic patients are also at high risk of health-care-associated infections; when bacteremia occurs, there can be seeding to the joints. There has been a report of septic arthritis arising from catheter-associated Staphylococcus epidermidis bacteremia in a neutropenic patient . In prolonged neutropenia, fungal infections may ensue and so can infectious arthritis from fungal organisms such as Candida spp. . and Pseudallescheria boydii .
Patients who are immunocompromised because of defects in cell-mediated immunity are predisposed to infections caused by intracellular bacteria, fungi, and mycobacteria. These include patients infected with the human immunodeficiency virus (HIV). Musculoskeletal disorders in patients with HIV may be due to a direct effect of the virus, opportunistic infections, or noninfectious complications of HIV infection or its therapy . Various conditions can be seen in the setting of HIV, including painful articular syndrome, reactive arthritis, HIV-associated arthritis, rheumatoid arthritis, hypertrophic osteoarthropathy, acute gout, avascular bone necrosis, septic arthritis, and osteomyelitis . Similar to HIV-negative patients, septic arthritis occurring in HIV-infected patients is most commonly due to S. aureus . There have also been reports of septic arthritis caused by mycobacteria in patients infected with HIV .
In the modern era of highly active antiretroviral therapy, patients infected with HIV rarely now present with opportunistic infections; joint swellings in HIV patients may be due to noninfectious complications rather than septic arthritis as in the past before effective treatment options were available for HIV disease.
Transplant patients are particularly prone to septic arthritis caused by unusual organisms. In the first few weeks after transplantation, joint infections are often hematogenous and caused by health-care-associated pathogens such as S. aureus (including MRSA) and gram-negative bacilli including P. aeruginosa . However, in the months following transplantation, as patients are maintained on immunosuppressive therapy, they are more prone to infections caused by fungi and mycobacteria.
Endemic fungi, including Histoplasma capsulatum , Blastomyces dermatitidis , Coccidioides immitis , and Penicillium marneffei , are present in certain geographic regions. After transplantation, patients may manifest disease after primary exposure or through reactivation of latent infection . The most frequently implicated endemic fungal infection in the solid organ transplant population in the United States is histoplasmosis , and it has been transmitted to solid organ recipients via the transplanted organ . The above mentioned infections are commonly disseminated and have been reported to seed to bones and joints .
Mycobacterial septic arthritis is extremely common in the developing world due to the high prevalence of Mycobacterium tuberculosis . M. tuberculosis is the most common infectious disease in adults worldwide, with an estimated 1.5 billion people with latent tuberculosis infection. This infection is often acquired through the airborne route and reaches the bone and joints via hematogenous or lymphatic spread. As a result, the most common joints involved in septic arthritis due to tuberculosis are in the axial skeleton . Tuberculous vertebral osteomyelitis or Pott’s disease is a major cause of morbidity worldwide . The most common site is the thoracolumbar junction, but any segment of the spine can be involved. An uncommon site of spinal tuberculosis is the atlantoaxial junction, but infection in this site can have devastating consequences .
The appendicular skeleton is also at risk of tuberculous infections – primarily in developing countries where there is heavy exposure to the pathogen. Tuberculous arthritis commonly affects large weight-bearing joints such as the hip and knee. This is due to better perfusion of muscle insertions at these large joints, which allows mycobacteremia to seed in these joints . Joints such as the shoulder, ankle, elbow, and wrist are infrequently involved, and joints such as the sternoclavicular, acromioclavicular, sacroiliac, pubic symphysis, and small joints of the hands and foot are very rarely involved , with only occasional case reports of tuberculosis affecting bones of the foot .
In the developed world, the rate of tuberculosis has declined dramatically since the advent of effective chemotherapy and good public health measures. As a result, tuberculous arthritis is seen mainly in immunocompromised individuals. These include, for example, patients who are infected with HIV and patients who are treated with biologic agents.
For prosthetic joint infections, the microbiologic etiology and clinical presentation may vary according to whether the infection is early (within 3 months after surgery), delayed (3–24 months after surgery), or late (more than 24 months after surgery). Staphylococci are the most frequently isolated organisms at all timepoints – early, delayed, and late – with coagulase-negative staphylococci accounting for most of these (30–41%) and S. aureus as the second most common (12–39%) . Early infections are usually caused by more virulent organisms such as S. aureus and gram-negative bacilli, delayed infections are usually caused by less virulent organisms such as coagulase-negative staphylococci and Propionibacterium acnes , and late infections are usually caused by hematogenous seeding of a variety of organisms depending on the source of the infection .
Infectious complications associated with biologic therapies have been described since their introduction in recent years for the treatment of rheumatologic disorders and other inflammatory conditions .
The risk of developing septic arthritis among patients with rheumatoid arthritis was specifically studied by Galloway and his colleagues when they compared the risk of septic arthritis between 11881 anti-TNF agent-treated and 3673 non-biological disease-modifying antirheumatic drug-treated patients . They found that the use of anti-TNF therapy was associated with a doubling of the risk of septic arthritis. The risk was the same for the three agents studied – adalimumab, etanercept, and infliximab – and was highest in the early months of therapy. The knee joint was the most frequent site of involvement in both the cohorts. S. aureus was the most common causative pathogen in both the cohorts. Other organisms that were seen in the anti-TNF cohort included Listeria monocytogenes , non-typhoidal Salmonella spp., and P. aeruginosa . This is consistent with prior case reports, implicating these less common intracellular organisms: L. monocytogenes and Salmonella enteritidis .
Rituximab is a monoclonal immunoglobulin G1 antibody that targets CD20 on B lymphocytes, and its use results in depletion of these B lymphocytes for 6–9 months . Rituximab has been linked to a wide spectrum of infectious complications including septic shock and bacteremias , but the actual incidence of septic arthritis associated with rituximab use is not as well defined as with the anti-TNF agents. There are mainly case reports of hip septic arthritis and septic polyarthritis with Ureaplasma urealyticum .
Anti-interleukin-1 agents include anakinra and rilonacept. A meta-analysis by Salliot et al. found that the risk of serious infectious increased when a high dose of anakinra was used. Among the serious infections occurring in anakinra-treated patients were osteomyelitis, cellulitis, bursitis, infected bunion, and gangrene . Experience with rilonacept is still limited, although the rilonacept package insert reported a case of nontuberculous mycobacterial olecranon bursitis in a patient receiving rilonacept for an unapproved indication in combination with intra-articular glucocorticoid injections .
Abatacept is a fully human soluble fusion protein, which downregulates T-cell activation. A meta-analysis by Salliot et al. did not find a significant increase in serious infections in patients with rheumatoid arthritis treated with abatacept . However, its use is relatively recent, and there have been case reports of infections caused by Nocardia and a number of viral infections in patients treated with abatacept. Alemtuzumab, an anti-CD52 agent, is associated with a wide spectrum of infectious complications, including invasive fungal infections and severe mycobacterial infections , but there are limited data on the extent of the association with septic arthritis per se. There have been case reports but no quantification of the risk to our knowledge.
The clinical features of acute septic arthritis of native joints are acute joint pain, swelling, warmth, erythema, decreased range of motion, fever, and malaise . As with any other condition, evaluation begins with detailed history taking, with a focus on determining the presence of risk factors described above. A long list of differential diagnoses exists for septic arthritis, including traumatic effusion, hemarthrosis, crystal arthropathy, bursitis, cellulitis, and transient synovitis of unknown etiology .
Classical symptoms and signs are more subtle in children – they may present with simply irritability, anxiety, failure to thrive, tachycardia, and anemia . The hip joint is the most common joint for septic arthritis in children. In particular, an atraumatic irritable hip in children has several other differential diagnoses besides septic arthritis of the hip: transient synovitis, Perthes’ disease, slipped upper femoral epiphysis, juvenile rheumatoid arthritis, bone tumors, sickle cell crisis, and referred pain . A prospective study found that fever (oral temperature >38.5 °C) was the best predictor of septic arthritis, followed by an elevated C-reactive protein (CRP) level, an elevated erythrocyte sedimentation rate (ESR), refusal to bear weight, and an elevated serum leukocyte count .
Early prosthetic joint infections usually present with acute onset of fever, persistence of pain, swelling, effusion, erythema, and warmth at the implant site, whereas delayed prosthetic joint infections present more subtly with implant loosening or persistent joint pain. Late infections occasionally present with an acutely inflamed joint that may be associated with systemic features of sepsis .
For immunocompromised patients, symptoms may be very nonspecific and a careful clinical examination is needed to detect subclinical septic arthritis. This could be part of a workup of fever in an immunocompromised patient in which only subtle joint swelling is elicited or spinal tenderness may be the only clue to a discitis or other infection of the axial skeleton.
In a retrospective study of community-acquired septic arthritis from tropical Australia , hip infections were more common in people younger than 15 years of age and knee infections in those older than 45 years of age. Others have found similar distributions .
Atypical joint infections (costochondral, sacroiliac, and sternoclavicular joints) have been associated with intravenous drug abuse or other hematogenous sources. Sternoclavicular septic arthritis is uncommon in the general population but has been documented much more frequently in intravenous drug abusers . Rarely, sternoclavicular septic arthritis can also result from infected central lines . The sacroiliac joint is the most common site of skeletal involvement in adult brucellosis.
Septic arthritis of the hand commonly follows bite–fight wounds or clenched fist injuries where there is perforation of the skin and hand joints. Often, this results in severe septic arthritis of the third metacarpal joint of the dominant hand . This is often accompanied by deep space infections in the hand, necessitating a hand surgery consultation . A history of bites and fights needs to be elicited when dealing with patients who present with septic arthritis of the hand, although this might not be forthcoming. As septic arthritis of the fingers is usually caused by bites, organisms that are a part of the oral flora of humans or animals are the common causative agents.
In immunocompromised patients, Mycobacterium marinum and other atypical mycobacterial infections can occur in patients with exposure to fish or aquatic environments . These can also occur in immunocompetent individuals . Also, penetrating trauma, including local corticosteroid therapy, may cause septic arthritis in atypical joints . Septic arthritis of the feet most commonly occurs in those with diabetes, other forms of peripheral neuropathy, or spinal cord lesions or those with vasculopathy – either arterial or venous. Evaluation would include eliciting a history of the underlying medical conditions, including history of neuropathy, claudication, peripheral edema, skin changes, or other signs and symptoms of chronic arterial or venous insufficiency.
Acute monoarticular arthritis due to a hematogenous source most commonly affects the knees in adults, as described above, although hip joints are affected more commonly in young children. They present with painful, acutely tender, swollen knees with erythema, tenderness, and limitation of movement on examination. Differential diagnosis would include bursitis or soft tissue infections, although a careful physical examination usually allows for a distinction between these entities.
Vertebral osteomyelitis can be associated with a septic arthritis of the facet joints or more commonly a discitis. A comprehensive review of vertebral osteomyelitis is beyond the scope of this review, but it is important to note that septic arthritis of the axial skeleton is very difficult to diagnose clinically. The presentations are often protean, and patients may have very limited localizing symptoms, with only persistent fever and vague back or neck pain.
The diagnosis of septic arthritis is primarily clinical; however, it can be supported by laboratory evidence. Laboratory investigations can be divided into systemic and specific tests.
For systemic tests, peripheral leukocyte counts are frequently obtained and patients with septic arthritis often have leukocytosis. However, this has low sensitivity and specificity .
Inflammatory markers are widely used by clinicians to diagnose septic arthritis. ESR has been used for more than a 100 years in the diagnosis of infections, but its role in septic arthritis is limited, especially in individuals with rheumatic diseases who may have a high ESR due to their underlying rheumatological conditions. In patients with native joints without underlying hematological or rheumatological conditions, ESR can be useful . Serial ESR measurements are used to define the duration of therapy for patients on long-term antibiotic therapy for septic arthritis, especially with prosthetic joint infections.
CRP is typically elevated in acute bacterial arthritis but as we know in clinical practice, this is not specific as many other conditions can also cause CRP to be elevated. At the same time, we should not exclude a diagnosis of septic arthritis because the CRP is not elevated. In patients with underlying rheumatological conditions, there is significant overlap in diagnostic values of CRP and ESR for septic and inflammatory arthritis. Hence, even though there is some data suggesting that the inflammatory markers can used to distinguish septic arthritis from flares of inflammatory conditions , our clinical experience suggests that clinical judgment is the most important factor in making this differentiation. A sudden increase in inflammation in one or two joints out of proportion to disease activity should raise the suspicion of superimposed bacterial arthritis .
Procalcitonin was shown in a prospective study of 78 Thai patients with acute arthritis to have a sensitivity and specificity of 59.3% and 86% respectively for the diagnosis of bacterial septic arthritis when a cutoff of 0.5 ng/ml was used .
Radiology is rarely helpful in the diagnosis of septic arthritis . Plain X-rays do not reliably distinguish septic arthritis from inflammatory arthritis unless there are classic features, for example, of gouty arthritis, although these can coexist with septic arthritis in some individuals .
Ultrasound performed by an experienced musculoskeletal radiologist has been reported as being able to identify cases of septic arthritis although in practice, few would use ultrasound for this purpose in the modern era.
Similarly to plain X-rays, computed tomography (CT) scans have limited use during the early stages of septic arthritis. However, the advantage of CT over plain films is that CT may allow visualization of joint effusion, soft tissue swelling, and para-articular abscesses. CT is more sensitive than plain X-rays in the imaging of joint space widening because of localized edema, bone erosions, and foci of osteitis and scleroses . There are artifacts that can limit the use of CT scans for prosthetic infections, but sometimes periprosthetic collections can be revealed in CT scans .
Magnetic resonance imaging (MRI) is sometimes useful in native joint septic arthritis , but its role in prosthetic joint infections is limited primarily by scatter, although newer MRI scanners are less affected by implants and can actually define prosthetic infections, especially with associated collections and sinus tracts.
Positron emission tomography scans have very limited data on their role in the diagnosis of both native and prosthetic joint infections .
Bone scintigraphy is a very sensitive method in detecting bone and joint infections, but it is not specific as it rarely is able to distinguish infection from other pathology. Labeled leukocyte scan has a role to play in the diagnosis of prosthetic joint infections as MRI has a lesser utility .
Aspiration of the joints is classically done to diagnose joint infections in large joints, both native and prosthetic . The aspiration of pus has typically been seen as diagnostic of infection from the pre-antibiotic era . Margaretten et al. have demonstrated in a systematic review that the combination of synovial fluid leukocyte count and percentage neutrophils was the best tool to predict bacterial arthritis before culture results became available . The higher the synovial fluid leukocyte count, the greater the likelihood of septic arthritis. In patients who are immunocompromised , who have been partially treated with prior antibiotics or who have prosthetic joints , the synovial fluid leukocyte count may be lower.
There are some intriguing preliminary data to show that a combination of leukocyte esterase and glucose strips can be used to diagnose septic arthritis rapidly at the point of care . This has a positive predictive value of 94% and a negative predictive value of 98%, which is very promising if validated.
Gram stain has a sensitivity and specificity of 37% and 99% respectively, but in the modern era when patients present early, specimens obtained from joint aspiration are often gram-stain negative .
Cytology is often performed during joint aspiration of acute arthritis primarily to exclude gouty or other crystal arthritides, although sometimes atypical organisms such as mycobacteria or fungi can be identified in cytopathologic specimens obtained by joint aspiration .
Cultures are the gold standard for the diagnosis of septic arthritis – for both native and prosthetic joints . These are usually done using standard media, but there is the need for selective media for gonorrhea, mycoplasma, and tuberculosis, although molecular diagnostic tests have been used for gonorrhea and tuberculosis with good sensitivity and specificity.
Aspiration of joints and injection of the aspirate into blood culture bottles is widely used in prosthetic joints, and it increases the sensitivity but at the potential expense of reduced specificity with possible contamination due to breaks in aseptic practices .
Sonication of whole explanted joints is widely used for prosthetic joint infections, especially by the group at the Mayo clinic .
The polymerase chain reaction in addition to its use in tuberculosis and atypical infections has also been widely used for the diagnosis of prosthetic joint infections. More recently, 16S rRNA gene sequencing is becoming increasingly employed in bacterial identification.
CT- or ultrasound-guided biopsy is used primarily for septic arthritis of atypical joints such as in the axial skeleton or in sternoclavicular septic arthritis . Open biopsy has obviously the highest sensitivity and specificity in native joint septic arthritis, but it is rarely done. Arthroscopy is widely used for the diagnosis of septic arthritis of the knee, and it can have a therapeutic role .