Differential Diagnosis and Patient Presentation

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arthritis when emergency surgical intervention is deemed necessary.

Differential Diagnosis, Clinical Presentation, and Causative Organisms

The differential diagnosis of an acutely painful joint is broad and includes crystalline and inflammatory arthritides, trauma, neoplasm, and infection. Patients with septic arthritis classically present with fever, chills, and a warm, erythematous, swollen, and painful joint. However, variation in patient presentation necessitates a high index of clinical suspicion for septic arthritis. Patients present with high-grade fever in only 58% and serum leukocytosis in only 50–60% of cases [4].

Many risk factors predispose patients to septic arthritis (Table 1). Coexisting primary rheumatologic disorders have been reported in as many as 50% of patients with bacterial arthritis [5]. Rheumatoid arthritis may increase the risk of septic arthritis as much as 15-fold [6], owing to a combination of preexisting joint damage, baseline immune dys- regulation, and use of immunomodulatory therapy, such as tumor necrosis factor inhibitors [7]. Both infection and acute exacerba- tion of a chronic joint disorder may present with joint pain and swelling.

The most common causative agent of adult septic arthritis is Staphylococcus au- reus, which accounts for more than 50% of cases [4] (Fig. 1). The incidence of methicillin-resistant S. aureus infection is on the rise in the United States. Coagulase-negative

Septic Arthritis: An Evidence- Based Review of Diagnosis and Image-Guided Aspiration

Brian Y. Chan¹ Amanda M. Crawford Patrick H. Kobes Hailey Allen Richard L. Leake Christopher J. Hanrahan Megan K. Mills

Chan BY, Crawford AM, Kobes PH, et al.

1All authors: Department of Radiology and Imaging Sciences, University of Utah School of Medicine, 30 N 1900 E, Rm 1A071, Salt Lake City, UT 84132-2140.

Address correspondence to B. Y. Chan ([email protected]).

AJR 2020; 215:568–581

ISSN-L 0361–803X/20/2153–568

S

eptic arthritis is an emergency that can cause rapidly progressive and irreversible damage to the affected joint, resulting in se- rious morbidity and mortality. The incidence of septic arthritis ranges from approximately 2 cases per 100,000 people per year [1] to 20 cases per 100,000 people per year in low-in- come settings [2]. Its presentation varies by patient demographics and is confounded by preexisting comorbidities. Radiologists should be equipped to counsel the ordering provider regarding the role of preinterven- tion imaging. Familiarity with clinical presentation and laboratory assessment can help the radiologist guide patient selection for percutaneous aspiration. When arthrocentesis is pursued, understanding the technical considerations of the procedure and subse- quent fluid analysis can minimize patient risk and maximize diagnostic yield. Despite the important role radiologists play, clinical workflow varies widely by practice setting [3]. Review of the current state of knowledge is warranted to adopt an evidence-based approach to the diagnosis and management of septic arthritis.

Preaspiration Assessment

Appropriate patient selection before joint aspiration is a complex process with many variables. Appendix 1 summarizes the considerations before arthrocentesis discussed in this review. On occasion, joint aspiration may be deferred in the evaluation of septic

Keywords: arthrocentesis, aspiration, interventional, periprosthetic joint infection, septic arthritis doi.org/10.2214/AJR.20.22773

Received January 1, 2020; accepted after revision February 26, 2020.

FOCUS ON:

OBJECTIVE. The purpose of this evidence-based review is to equip radiologists to discuss and interpret findings obtained with various imaging modalities, guide patient selection for percutaneous aspiration, and safely perform arthrocentesis to assess for infection in both native and prosthetic joints.

CONCLUSION. Septic arthritis is an emergency that can lead to rapidly progressive, irreversible joint damage. Despite the urgency associated with this diagnosis, there remains a lack of consensus regarding many aspects of the management of native and periprosthetic joint infections.

Chan et al.

Septic Arthritis Musculoskeletal Imaging Review

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s taphylococci are often contaminants but can cause clinically mild, indolent infections after orthopedic procedures. The incidence of streptococcal and gonococcal septic arthritis has declined over the past few decades. Gram- negative rods typically affect elderly patients and young IV drug users. Atypical mycobac- terial, viral, and fungal infections also occur, particularly in immunosuppressed patients.

Serum Laboratory Evaluation

Serum laboratory evaluation for septic arthritis includes peripheral WBC count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level. However, the results of these laboratory tests are in- adequately specific to substantially alter the pretest probability of septic arthritis [8, 9].

Absence of leukocytosis or elevated ESR or CRP level does not exclude a diagnosis of septic arthritis [10]. Measurement of procalcitonin has had diagnostic performance su- perior to that of traditional serum laboratory tests in assessing septic arthritis [11, 12];

however, procalcitonin level is insufficient to differentiate periprosthetic joint infection (PJI) from aseptic loosening [13]. ^d-Dimer is a promising serum biomarker for early detection of PJI; the test had higher sensitivity and specificity than both ESR and CRP in one study [14]. Unlike ESR and CRP levels,

d-Dimer level rapidly increases and returns to baseline after elective total knee or hip arthroplasty, making it a potential tool in the early detection of PJI [15]. Table 2 summarizes commonly used cutoff values in standard serum laboratory evaluation.

Although synovial fluid culture is considered the reference standard for diagnosing septic arthritis [9], blood cultures can play a crucial role and are recommended as part of the initial diagnostic evaluation for septic arthritis [16]. Hematogenous spread is the most common avenue of joint infection [8],

and treatment of septic arthritis in patients with negative synovial fluid culture results can instead be directed at an organism cul- tured from the bloodstream. Blood cultures have been reported to be the only test to identify an organism in 9–14% of cases of septic arthritis [1, 17].

Preaspiration Imaging

Preaspiration imaging can aid evaluation of osseous structures and surrounding soft tissues. Radiography is appropriate as the first imaging study, particularly for patients who have undergone prior surgery to evaluate existing hardware [18]. Radiograph- ic findings are usually normal in early septic arthritis or may reveal periarticular osteope- nia. More advanced infections may present with nonspecific erosions or uniform joint space narrowing [19, 20] (Figs. 2 and 3).

MRI is complementary to aspiration [18]

and can reveal a joint effusion or deep soft- tissue infection. Nonspecific bony erosions, marrow edema, and articular cartilage de- struction can be seen with septic arthritis (Figs. 2B, 3D, and 3E) but also with in-

flammatory arthropathy [21]. Notably, 16%

of septic joints in one study [21] contained a subjectively normal amount of fluid; however, the study did not specifically address sit- uations in which imaging evidence of joint fluid was completely absent. IV contrast administration can reveal synovial enhancement, abscesses, and epiphyseal involvement in children but does not increase sensitivity or specificity for septic arthritis [22].

Preaspiration ultrasound (US) can help confirm the presence of a joint effusion (Fig. 3B) and assess for fluid collection in the overlying soft tissues [23], although this approach is operator and resource dependent.

A potential argument ordering providers make against advanced preaspiration imaging is concern over delaying definitive management and causing progressive, irreversible cartilage loss. In animal models, cartilage loss is seen as early as 24 hours after joint infection, and permanent cartilage injury oc- curs within 3–4 days [24]. Lauper et al. [25]

challenged the necessity of immediate surgical lavage and found similar functional outcomes among patients who underwent joint TABLE 1: Risk Factors for Septic Arthritis

Preexisting Joint Diseases Skin Diseases Medical Conditions Medication-Induced Conditions Other Rheumatoid arthritis Psoriasis Diabetes mellitus Chronic systemic corticosteroid

therapy (e.g., prednisone) Prior joint arthroplasty Crystalline deposition arthropathies

(gout and calcium pyrophosphate deposition)

Eczema Cirrhosis Disease-modifying antirheumatic

drugs IV drug use

Osteoarthritis Skin ulcers End-stage renal disease Intraarticular corticosteroids Alcoholism Systemic lupus erythematosus Skin infection HIV infection, AIDS, and other

immunosuppressed states Other immunosuppressive

medications Human bite (fight bite)

Trauma Bacteremia Low socioeconomic status

Recent surgery Advanced age

TABLE 2: Sample Cutoff Values for Commonly Used Serum and Synovial Fluid Tests

Test

Sample Cutoff Value

Native Joint Chronic Periprosthetic Joint Infection Serum

WBC count (/µL) > 11,000

C-reactive protein level (mg/dL) > 2 > 1 Erythrocyte sedimentation rate (mm/h) > 30 > 30 Procalcitonin (ng/mL) > 0.3

d-Dimer level (ng/mL) > 860

Synovial fluid

WBC count (/µL) > 50,000 > 3000 Polymorphonuclear leukocytes (%) > 75 > 80

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lavage less than 6, 6–12, 12–24, and more than 24 hours after presentation. The need for urgent intervention is balanced by the risk of missing unexpected pathologic conditions. Patients without preoperative imaging who are later discovered to harbor extraarticular infection may need repeat operations to rectify inadequate treatment [24, 26]. Abbre- viated MRI protocols entailing solely fluid- sensitive sequences are highly sensitive for musculoskeletal abnormalities [27, 28] and may shorten the delay to treatment while still enabling comprehensive preoperative evaluation. Ultimately, the decision to perform imaging before aspiration should be based on an individualized assessment and discussion with orthopedic colleagues.

Special Considerations

Prosthetic joints—Suspected PJI in a patient in hemodynamically stable condition does not require immediate aspiration be- cause of the absence of cartilage [29]. How- ever, PJI should be considered urgent and is a major cause of postarthroplasty failure and ongoing pain. PJI can be acute or chronic; traditionally, these were differentiated by amount of time elapsed since surgery (for example, acute infections occurring within 4 weeks of surgery [30]). It is now agreed that PJI is a continuum that culminates in estab- lishment of a chronic biofilm, and the time to biofilm maturity depends on both the bacterial species and the host [31]. Chronic PJI is more common and often presents with pain or functional deterioration [32]. Unlike the situation with aseptic prosthetic loosening, pain is unrelated to activity and is present at rest. Overt signs, such as fever, regional warmth, and erythema, are frequently absent. A more specific sign of PJI is evidence of deep soft-tissue involvement, including a sinus tract, purulence, abscess, or extensive necrosis. Patients with multiple prosthetic joints found to have one infected prosthesis are at increased risk of a second PJI, and clinical assessment of all prosthetic joints is important to determine the need for additional aspirations [33].

Compared with septic arthritis in native joints, PJIs are often characterized by less virulent pathogens: 50–60% of hip and knee PJIs are caused by S. aureus and coagulase- negative staphylococci (e.g., Staphylococcus epidermidis). In the upper extremity, coagulase-negative staphylococci account for approximately 40% of shoulder and elbow PJIs.

Propionibacterium acnes is present in 24%

of shoulder PJIs [34], in which sebum-rich hair follicles in the axilla likely promote col- onization [35]. Organisms are typically en- meshed in a biofilm covering the prosthesis, which protects them from the host immune system and antibiotics [36]. These characteristics make PJI a difficult clinical diagnosis. Several subspecialty societies have developed diagnostic criteria and algorithms to facilitate evaluation [37–40], and the Sec- ond International Consensus Meeting on Or- thopedic Infections was convened to provide expert consensus given the heterogeneity in practice [41]. Recommendations in these various guidelines were recently assessed to es- tablish updated, evidence-based diagnostic criteria and algorithms for the evaluation of PJI [42] (Fig. 4). Elevation of either ESR or CRP level should prompt joint aspiration; if both ESR and CRP levels are within normal limits, PJI is extremely unlikely [39]. Given that PJIs are characterized by sessile rather than free-floating bacteria, blood cultures are not included in the definition of PJI.

Radiographs may reveal periprosthetic os- teolysis but are frequently normal [43]. Al- though radiographic findings are nonspecific in the early postoperative period, radiographic evidence of soft-tissue gas more than 14 days after total knee arthroplasty was predictive of early PJI in a recent study [44] and may her- ald a broader spectrum of microorganisms than typically encountered. Triple-phase bone scintigraphy and WBC scintigraphy are highly sensitive for infection and can be useful in confounding cases. PJI is highly unlikely in the absence of radiotracer uptake [40]. Hybrid imaging techniques such as ¹⁸F-FDG PET/CT and ^99mTc-antigranulocyte SPECT/CT can be used to improve localization of radiotracer uptake, although their lack of specificity limits their routine use at our institution. MRI and CT are not routinely advocated for PJI, be- cause aspiration and culture are needed re- gardless of advanced imaging findings (Fig. 5).

Children—Clinical tools have been inves- tigated for differentiating septic arthritis from similarly presenting nonsurgical pediatric di- agnoses, such as juvenile idiopathic arthritis, transient synovitis, and Lyme disease [45–50].

Slipped capital femoral epiphysis and Legg- Calve-Perthes disease are other important diagnostic considerations in pediatric patients with hip pain. Trauma is an additional con- founder; recent falls precede approximately 20% of osteoarticular infections [51].

Communication barriers may preclude a comprehensive patient interview. Neonates

can present with irritability and listlessness, whereas toddlers may acknowledge nonspecific pain [52]. Physical examination may reveal guarding, limited range of motion, and inability to bear weight. Laboratory evaluation is likewise limited; leukocytosis is less common in younger children and rare in neonates [52]. Kocher et al. [46] identified four criteria—history of fever, inability to bear weight, WBC count greater than 12,000/μL, and ESR greater than 40 mm/h—to differentiate septic arthritis from transient synovitis.

Another study [53] applying the criteria proposed by Kocher et al. did not reproduce the originally reported high predictive value.

A threshold CRP greater than 2.0 mg/dL has been found to have higher predictive value for septic arthritis than does leukocytosis, elevated ESR, or refusal to bear weight [45].

Additionally, Kingella kingae, an increas- ingly recognized cause of septic arthritis in children younger than 4 years [54, 55], has a milder clinical course often mistaken for a noninfectious pathologic condition and is notoriously difficult to detect with standard laboratory techniques [56]. The addition of oropharyngeal swabs and polymerase chain reaction assays for K. kingae can help identify the causative organism in osteoarticular infections [56].

Children with septic arthritis often have concomitant osteomyelitis and adjacent musculoskeletal infections [57–59], in part due to anatomic differences that facilitate spread of osteomyelitis into the adjacent joint. Ro- bust transphyseal vessels in neonates al- low communication of the metaphysis with the adjacent nonossified epiphysis and joint.

After these vessels involute in early childhood, the metaphysis remains intraarticular in some long bones (e.g., proximal humer- us and radius, proximal femur, distal fibula), and metaphyseal subperiosteal infection or abscess can progress to deposition of purulent material within the joint [60]. Schallert et al. [61] found that 75% (41/55) of children with metaphyseal osteomyelitis and adjacent joint effusion ultimately were found to have surgically confirmed septic arthritis. Those authors concluded that children with joint effusions associated with metaphyseal osteomyelitis should be presumed to have septic arthritis [61].

Rosenfeld et al. [26] proposed an algorithm including five clinical and laboratory variables to identify patients at high risk of adjacent infections who could benefit from preoperative MRI, although the generaliz-

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ability of these criteria to other populations has been questioned [62]. Investigators in several studies [63–65] and 88% of Interna- tional Consensus Meeting delegates advocate percutaneous or open juxtaarticular bone biopsy at the time of aspiration in children to confirm the diagnosis of osteomyelitis and increase sensitivity for an organism when synovial fluid culture results are negative.

Immunosuppression—Immunosuppres- sion is a relative risk factor for septic arthritis and is associated with many chronic conditions, including diabetes mellitus, rheumatoid arthritis, and HIV infection [66]. Anti–tumor necrosis factor therapy in patients with rheumatoid arthritis doubles the risk of septic arthritis [7]. Other medications, such as corticosteroids and disease-modifying antirheumatic drugs, may also induce an immunocompromised state. Immunosuppressed patients can have an atypical presentation of a blunted pain response [67]. Immunosuppressed patients also have theoretic differences in laboratory values due to difficulty mounting a normal immune response. Butler et al. [68], however, found no significant difference in laboratory values between immunosuppressed and immunocompetent patients with septic arthritis. Notably, procalcitonin levels are unaffect- ed by steroids [69] and may be a helpful biomarker in this population.

Possible Contraindications to Percutaneous Aspiration

Anticoagulation—There is little consensus in the literature [70] or anecdotally [3] regarding the handling of anticoagulation before arthrocentesis. Porrino et al. [3] reported that 39% (96/247) of surveyed radiologists agreed that coagulopathy should be correct- ed before arthrocentesis. However, the avail- able literature supports the notion that clinically significant bleeding complications after both blind and image-guided arthrocentesis in patients undergoing anticoagulation are ex- ceedingly rare [71–74]. A 2017 retrospective study [74] showed no bleeding complications following 1050 consecutive procedures over 6 years on patients using direct oral anticoagulants (e.g., direct thrombin inhibitors and direct factor Xa inhibitors) during arthrocentesis. In addition, there is a real risk of inciting thromboembolic events when interrupting anticoagulation [75]. Overall, percutaneous joint access is considered low risk [76, 77], and at our institution we do not routinely discontinue anticoagulation or perform preprocedural co- agulation tests before arthrocentesis.

Recent antibiotic administration—Simi- lar to the situation with blood cultures [78], the yield of synovial fluid cultures decreases after antibiotic administration. Barrack et al.

[79] found that 7 of 12 patients (58%) taking antibiotics who had no growth at initial knee aspirations ultimately had a diagnosis of septic arthritis. Hindle et al. [80] found a combined decrease in synovial fluid culture sensitivity from 79% to 28% in both native and prosthetic knee aspirates after antibiotic administration. Despite the lower diagnostic value of microbiologic analysis after recent antibiotic use, no guidelines have been estab- lished regarding duration of antibiotic cessation before arthrocentesis. At our institution we do not typically defer joint aspiration after recent antibiotic administration.

In the setting of prior arthroplasty, a lon- ger interval between antibiotic cessation and aspiration can increase the likelihood of culture positivity. Malekzadeh et al. [81] determined that antimicrobial therapy within 3 months was associated with increased likelihood of culture-negative PJI (odds ratio, 4.7).

Both American Academy of Orthopedic Sur- gery [39] and Infectious Disease Society of America [38] guidelines call for withhold- ing antibiotics for at least 2 weeks before at- tempting joint aspiration in patients with suspected PJI.

Overlying cellulitis and other concomitant infections—A dreaded risk of arthrocentesis is inducing septic arthritis in a previously aseptic joint. Rates of septic arthritis after intraarticular steroid injection are as low as 1 in 10,000 [82, 83]. Although intuitively the presence of overlying cellulitis increases the risk of inducing septic arthritis, there is an absence of literature confirming the risk of seeding a sterile joint with a needle that has traversed a soft-tissue infection [33]. Despite this, there is no shortage of expert opinions endorsing [23, 70, 84] and discounting [33, 85] cellulitis as a relative contraindication to arthrocentesis. A best attempt should be made to select a needle entry point that avoids the overlying soft- tissue infection, and deferring aspiration until the overlying infection is treated is a consid- eration. However, given the lack of high-level evidence, cellulitis is not considered an abso- lute contraindication [33]. Deeper soft-tissue infections (Figs. 6 and 7), such as abscess, bursitis, and pyomyositis, pose a greater chal- lenge. If fluoroscopic guidance is used for arthrocentesis, the radiologist may be unaware before entering the joint that an infected collection has been traversed.

Seeding of a sterile joint in patients with bacteremia is a theoretic risk. In a rabbit model, Olney et al. [86] found that septic arthritis developed in 30% of animals if blood drawn from a rabbit with bacteremia was in- jected directly into the joint. However, given that most cases of septic arthritis in adults are caused by hematogenous spread, patients with septic arthritis presumably have concurrent bacteremia.

Aspiration Considerations

Routine approaches to image-guided joint access are well described in the literature [70, 87]; however, in patients with infection or altered anatomy, the standard approach may present undesirable risks. Planning the optimal aspiration for an individual joint includes assessment of body habitus and visual inspection for signs of soft-tissue infection.

Review of preaspiration imaging can reveal normal structures susceptible to damage, soft-tissue infection, intervening obstacles, and osseous changes. Limitations in patient positioning may necessitate a nonstandard approach. Larger (e.g., 18- or 20-gauge) nee- dles are typically used for ease of aspirating thick purulent fluid.

Choosing an Imaging Modality for Needle Guidance

Selecting the ideal imaging modality for needle guidance relies on several factors, including patient age, body habitus, suspected pathologic condition, and the radiologist’s expertise in anatomy and percutaneous techniques. Although anticipated radiation dos- es are low, the radiologist should adhere to the goal of achieving as low as reasonably achievable radiation. Other influential factors include availability of equipment and ancillary staff, characteristics of the collection, and site of aspiration.

Fluoroscopic guidance is frequently used for joint access and may be preferred be- cause of operator proficiency, equipment availability, and decreased ionizing radiation relative to CT. Although soft-tissue and vascular structures are fluoroscopically occult, knowledge of basic anatomy can facilitate a needle approach that easily avoids major vascular structures.

US is useful for aspiration given its high sensitivity for joint effusion [88] (Fig. 8).

Other advantages include lack of ionizing radiation, visualization of vascular structures, differentiation of joint fluid from synovitis, identification of extraarticular fluid collec-

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tions [23], and ability to accommodate many patient positions and approaches. Mobile US units can be used for imaging of patients who are critically ill or in unstable condition for whom transport to the radiology department may be impractical or unsafe. US al- lows real-time needle visualization, which simplifies aspiration of thick or loculated collections and avoids extraarticular collections. However, US depends greatly on both operator and technologist comfort and skill.

US also has limited capacity for evaluating deeper structures and may be a poor choice for imaging of obese patients.

Occasionally, sonographic and fluoroscopic guidance may show insufficient anatomic detail for joint access. CT may be the preferred or safer modality, particularly in cases of irregular bony anatomy, presence of extensive heterotopic ossification, or proxim- ity of sensitive structures, such as mediasti- nal vasculature.

Choosing the Approach

Patients with osseous deficiency (e.g., extensive erosive change, prior surgery) may not have typical landmarks for joint access (Fig. 9). Preaspiration imaging can delineate the confines of the altered joint capsule. The osseous void in the expected location of the joint space can be targeted, although lack of a tactile backstop forces the operator to estimate the appropriate needle depth. Famil- iarity with anatomic alterations after surgery can be helpful in defining new approaches.

For example, in patients with a history of Girdlestone arthroplasty, one potential target for access is the midpoint of a line drawn between the greater and lesser trochanters [89].

In patients who have previously undergone arthroplasty, slight alterations to routine approaches can prevent overlapping metallic structures from obscuring the needle tip during fluoroscopic guidance. A frequently suc- cessful technique for aspirating a total hip prosthesis is to advance the needle until it contacts the lateral aspect of the neck of the femoral stem component and then direct the tip laterally off the component into the more dependent portion of the joint (Fig. 5C) [90].

Familiarity with the construction of the underlying hardware can aid intraarticular needle tip positioning, such as with a reverse total shoulder prosthesis (Fig. 10).

Local Anesthesia

Several commonly used agents for local anesthesia, including lidocaine, have been

reported to be bacteriostatic or bactericidal [91]. A 2018 study of common pathogens im- plicated in PJI [92] showed decreased growth in culture on exposure to 2% lidocaine. The presence of preservatives in commercial preparations of lidocaine and other anesthetics enhances this antimicrobial effect [93]. Caution is advised during arthrocentesis when instilling local anesthetics near the joint, and preservative-free lidocaine is preferred to maximize organism yield.

Confirmation of Intraarticular Positioning It is imperative to document intraarticular needle tip positioning, most importantly in the setting of a so-called dry tap to confirm the absence of obtainable fluid. Intraarticular positioning can be determined in real time if US is used for guidance. In the setting of fluoroscopic guidance, contrast instillation after aspiration can verify intraarticular needle positioning. Spread of iodinated contrast material (Fig. 3C) can show intraarticular communication with fluid collections, bursae, or sinus tracts. In prior studies, investigators have ex- pressed concern over the bactericidal effects of iodinated contrast material if inadvertently mixed with aspirated fluid, but this effect has not been found with modern low-osmolar and isoosmolar contrast agents [94]. Air contrast (Fig. 10B) is a cost-free alternative in patients with allergies to iodinated contrast material [95] but will introduce susceptibility artifacts if MRI is subsequently performed.

Deciding Whether to Perform Lavage

There is considerable debate regarding the role of joint lavage and reaspiration after initial failure to aspirate fluid. Kung et al. [96] described a hip lavage technique involving injection of 10 mL of iodinated contrast material or sterile nonbacterio- static saline solution with average return of 2.3 mL at reaspiration. Several studies have shown positive organism recovery by use of percutaneous joint lavage [96–98], and a 2018 study in the orthopedic literature [97]

showed similar performance between primary joint aspiration and reaspirated saline solution after dry tap in the diagnosis of PJI. Consensus statements generally ad- vise against saline lavage but are somewhat ambiguous; 83% of International Consensus Meeting delegates opposed the use of saline lavage but specified that performance by a radiologist was a possible exception [33]. Given the degree of uncertainty, discussion with orthopedic surgeons is recom-

mended before routine performance of this technique. Notably, aspirate obtained via saline lavage will yield a dilute sample [99], and the aspirate should be clearly labeled to avoid inaccurate cell counts.

Analysis of Aspirated Fluid

To prevent contamination, aspirate is often sent to the microbiology laboratory in the syringe used during the procedure. Howev- er, several studies [100–102] have shown increased pathogen yield when samples are in- oculated in blood culture bottles rather than as conventional cultures on standard agar me- dia. Although the minimum amount of requi- site fluid varies by institution, small volumes of aspirate can be sufficient for fluid analysis.

Our microbiology laboratory requires a mini- mal sample for culture and as little as 0.5 mL to determine cell count and differential.

Standard synovial fluid analysis includes culture and cell count and differential; crystal analysis is also often performed in the assessment of native joints in adults [103–106].

However, synovial WBC and polymorphonuclear leukocyte counts may remain elevated as long as 90 days after arthroplasty [107].

Additionally, cutoff values for abnormal synovial WBC count and polymorphonuclear percentage appear to vary for different joint sites [108, 109]. Table 2 includes potential cutoff values for common synovial fluid tests to assess for infection in both native and prosthetic joints. The presence of an adverse local tissue reaction can lead to falsely elevated synovial WBC counts and α-defensin levels, and intraoperative purulence can be present with either adverse local tissue reaction or PJI [33]. Samples should be incubated for at least 14–21 days to isolate slow-growing organisms associated with PJI [110]. Gram stain- ing is historically performed but has low diagnostic performance; the false-negative rate was 78% (111/143) in one study [111].

Additional biomarkers may be beneficial in equivocal cases. The most promising synovial biomarker at present appears to be α-defensin [112], which is an antimicrobial peptide released by neutrophils in response to infection and is detectable with the Synova- sure PJI test (Zimmer Biomet). Deirmengian et al. [113] reported that use of the combination of synovial α-defensin and CRP detect- ed with immunoassay led to correct diagno- ses of asepsis or infection in 99% of cases.

Leukocyte esterase reagent strips can provide a rapid estimate of synovial WBC count and have been included in diagnostic algorithms

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[114]. Newer molecular techniques, such as polymerase chain reaction [115], microarray analysis [116], and next-generation sequencing [117], are promising but require further validation before widespread adoption.

Dealing With Suspected False- Negative Results

A negative aspiration result (either dry tap or bland fluid) in a patient with suspected septic arthritis presents a clinical dilem- ma. Patients with clinically suspected septic arthritis but culture-negative synovial fluid have outcomes similar to those of patients with confirmed septic arthritis, supporting the rationale for treating patients as having presumptive septic arthritis even in the absence of confirmatory study results [118].

Several consensus statements endorse repeat aspiration for suspected hip PJI [33, 39].

The frequency of surgery for suspected PJI on patients with negative aspiration and positive intraoperative culture results was 22%

(219/996) in one large institutional retrospective review [119]. Another recent review revealed that repeat prosthetic hip joint aspiration within 90 days of the initial aspiration changed the diagnosis for 43% of patients (26/60) [120].

Despite uncertainty over the reliability of culture-negative aspiration results, there are no guidelines for the recommended time interval between or optimal number of repeat aspirations, and whether aspiration should be repeated should be driven by discussion between the radiologist and orthopedic sur- geon. Percutaneous synovial biopsy may have a role in this population. Coiffier et al.

[121] found that 27% (3/11) of patients with acute arthritis and inadequate synovial fluid for analysis had positive culture results after US-guided synovial biopsy.

Conclusion

Despite the urgency associated with a diagnosis of septic arthritis, there remains a lack of high-level evidence regarding many aspects of management of native and periprosthetic joint infections. This results in a heterogeneous approach to arthrocentesis across different practice settings. Under- standing the current literature will help the radiologist discuss challenging cases with ordering providers and adopt an evidence- based approach to joint aspiration. Ulti- mately, the best approach will be institution dependent and require interdisciplinary col- laboration between radiology, orthopedic

surgery, and other providers to maximize positive patient outcomes.

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1. Does the patient have a prosthetic joint?

2. Has the patient recently received antibiotic therapy?

3. Have blood cultures been obtained?

4. Review serum laboratory values: WBC count, erythrocyte sedimentation rate, C-reactive protein, ^d-Dimer.

5. Review prior imaging for underlying structural changes or intervening soft-tissue infection (e.g., abscess or bursitis).

6. Does the patient have any allergies?

7. Is the patient on anticoagulant therapy?

8. Does the patient have evidence of an overlying soft-tissue infection?

9. What imaging modality should be used for needle guidance? (Consider joint to be aspirated, assess body habitus.) APPENDIX 1: Considerations Before Joint Aspiration

Staphylococcus ≈ 56%

MSSA 42%

MRSA 10%

CONS 3%

Streptococcus ≈ 16%

Unspecified spp. 11%

Viridans streptococci 1%

S. pneumoniae 1%

Other spp. 3%

Gram-negative rods ≈ 16%

Pseudomonas aeruginosa 6%

Escherichia coli 3%

Proteus spp. 1%

Klebsiella spp. 1%

Others 4%

Others ≈ 12%

Polymicrobial 5%

Anaerobes 0.6%

Mycobacterium tuberculosis 1.8%

Neisseria gonorrhoeae 1.2%

Miscellaneous 4%

Fig. 1—Chart shows infectious agents in 505 cases of septic arthritis reported between 1999 and 2013. CONS = coagulase-negative Staphylococcus species;

MRSA = methicillin-resistant Staphylococcus aureus, MSSA = methicillin- sensitive S. aureus, spp. = species. (Data from [4]).

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A

Fig. 2—29-year-old man with septic arthritis of left knee.

A, Anteroposterior radiograph shows uniform joint space narrowing with articular surface irregularity (arrowheads). Marked soft-tissue swelling is evident around knee with effacement of fat planes lateral to distal femur and medial to proximal tibia.

B, Axial T1-weighted fat-suppressed contrast- enhanced MR image shows large joint effusion (star) with thick irregular synovial enhancement (straight arrows). Periarticular soft-tissue enhancement and intramuscular abscesses are present in gastrocnemius muscle (curved arrows).

B

C

A

Fig. 3—60-year-old man with septic arthritis of left hip.

A, Anteroposterior radiographs at baseline (left) and 2 months later (right) show rapidly progressive joint space narrowing and articular surface irregularity (arrowheads).

B, Oblique gray-scale ultrasound image shows complex hip joint effusion (star) and distention of joint capsule (arrowheads). Three milliliters of cloudy yellow fluid was aspirated, and synovial fluid analysis revealed WBC count of 166,000/μL with 97% polymorphonuclear leukocytes. Synovial fluid culture result was positive for methicillin-resistant Staphylococcus aureus. ACE = acetabulum, FH = femoral head.

C, Fluoroscopic image obtained during repeat hip joint aspiration shows intraarticular iodinated contrast material and multiple irregular filling defects (oval) suspicious for synovitis.

D, Axial T1-weighted MR image shows confluent hypointense marrow in femoral head and neck (star) and anterior cortical erosion (arrow) consistent with osteomyelitis.

E, Axial proton density–weighted fat-suppressed MR image shows exuberant marrow edema corresponding to region of abnormal T1 marrow signal intensity (star) in D.

Synchronous reactive or degenerative marrow edema in acetabulum (dashed arrow) retains hyperintense T1 marrow signal relative to skeletal muscle in D. Joint effusion (arrowhead) and fluid within greater trochanteric bursa (solid arrow) are also evident.

E D

B

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A Fig. 4—Proposed diagnostic tools for evaluation of suspected periprosthetic joint infection (PJI). CRP = C-reactive protein, ESR = erythrocyte sedimentation rate, LE = leukocyte esterase, PMN = polymorphonuclear leukocytes. (Reprinted from Journal of Arthroplasty, 34, Shohat N, Tan TL, Della Valle CJ, et al. Development and validation of an evidence-based algorithm for diagnosing periprosthetic joint infection, Pages 2730–2736.

A, Chart shows 2018 scoring-based criteria for PJI incorporating newer biomarkers and validated with patients with PJI as defined by Musculoskeletal Infection Society criteria.

(Fig. 4 continues on next page)