Evaluation and Management of Septic Arthritis and its Mimics in the Emergency Department

Septic arthritis is a dangerous medical condition associated with significant morbidity and mortality. However, the differential diagnosis can be broad with conditions that mimic this disease and require different evaluation and treatment. This narrative review presents the emergency medicine evaluation and management, as well as important medical conditions that may mimic this disease. Septic arthritis commonly presents with monoarticular joint pain with erythema, warmth, swelling, and pain on palpation and movement. Fever is present in many patients, though most are low grade. Blood testing and imaging may assist with the diagnosis, but the gold standard is joint aspiration. Management includes intravenous antibiotics and orthopedic surgery consult for operative management vs. serial aspirations. Clinicians should consider mimics, such as abscess, avascular necrosis, cellulitis, crystal-induced arthropathies, Lyme disease, malignancy, osteomyelitis, reactive arthritis, rheumatoid arthritis, and transient synovitis. While monoarticular arthritis can be due to septic arthritis, other medical and surgical conditions present similarly and require different management. It is essential for the emergency clinician to be aware how to diagnose and treat these mimics.


INTRODUCTION
Monoarticular arthritis is a common presentation to the emergency department (ED) and major cause of disability in the United States.Monoarticular arthritis has a wide range of potential etiologies, ranging from benign to life-threatening.One of the most concerning causes in a patient with monoarticular arthritis is septic arthritis.][6][7][8][9] Septic arthritis consists of a bacterial infection of the joint space that is associated with rapid joint destruction Brooke Army Medical Center, Department of Emergency Medicine, Houston, Texas The University of Texas Southwestern Medical Center, Department of Emergency Medicine, Dallas, Texas Rush University Medical Center, Department of Emergency Medicine, Chicago, Illinois * † ‡ within days if not adequately treated.[10] There are also a large number of conditions that may mimic septic arthritis, further confounding the diagnosis.

METHODS
We searched PubMed and Google Scholar for articles using the keywords "septic arthritis," "monoarthritis," "synovial fluid," "diagnosis," "treatment," and "emergency."Restricting the literature search to studies published in English, we found an initial 258 articles.We reviewed all relevant articles and decided by consensus which studies to include for the narrative review, focusing on articles investigating ED patients, studies evaluating synovial fluid results, and studies investigating septic arthritis diagnosis or management.A total of 133 articles were selected for inclusion in this review.We did not conduct Volume 20, no.2: March 2019 Evaluation and Management of Septic Arthritis and its Mimics in the ED Long et al.
a systematic review or meta-analysis, but rather a narrative review evaluating the emergency medicine investigation and management of septic arthritis and its mimics.

History and Examination
Obtaining an accurate history and assessment of risk factors can provide important clues to the diagnosis.A careful evaluation for risk factors can significantly change  8,9 Several of the findings were not available for pooling of data due to heterogeneity and unreliable methodology of included studies.[10][11]15,16 For example, patients with rheumatoid arthritis are at an increased risk for septic arthritis due to joint damage, poor skin condition, and immunosuppression. 26,29Rheumatoid arthritis complicated by septic arthritis is associated with poor outcomes including high morbidity and mortality. 10,29,30nterestingly, one study found that approximately 22% of all patients with culture-proven septic arthritis had no associated risk factors or underlying joint disease. 30This can be partly explained due to septic arthritis from N. gonorrhoeae in young patients with otherwise normal joints, though most cases of septic arthritis were due to S. aureus. 30atients traditionally present with a constellation of signs and symptoms including joint pain, tenderness to palpation, swelling, erythema, warmth, and painful or limited range of motion. 8,9,17The most common symptom is joint pain, which is found in 85% of patients. 8,9Joint swelling occurs in 78% of cases, 8,9 while joint tenderness has been suggested to be 100% sensitive. 6,7,15,17Fever > 39 o C occurs in up to 58% of patients, and the absence of fever should not be relied upon  *Remaining numbers represented by hyphens could not be calculated due to heterogeneity and unreliable methodology. 8,9ble 2. History and examination findings in septic arthritis.* 8,9valuation and Management of Septic Arthritis and its Mimics in the ED Long et al.
7,18 A joint with painful and limited active and passive range of motion is suggestive of intra-articular infection. 8,9boratory Testing Serum blood tests are inadequate to rule out septic arthritis.Synovial fluid is the gold standard test for making the diagnosis of septic arthritis.While a complete blood cell count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) are often obtained, the results of these tests will not sufficiently lower the post-test probability to influence the decision to obtain synovial fluid. 17,18 The s0,[35][36][37] One meta-analysis suggests a +LR of 1.3 (95% CI [1.1-1.8]) for ESR > 30 mm/hr. 9CRP > 10 mg/L also has a sensitivity approaching 90%; however, a level of 100 mg/L has a poor +LR of 1.6 (95% CI [1.1-2.5]). 8,9,35While procalcitonin demonstrates promise, at this time it requires further study before routine use. 8,10,17,18,38,39Blood cultures should be obtained in patients with septic arthritis, as they can help identify the source if the synovial fluid culture is negative.Blood cultures will be positive in over one-third of all patients, and 14% of patients with negative synovial fluid cultures will have positive blood cultures. 6,10,15,17,18

Imaging
Radiographs are typically obtained of the affected joint and may demonstrate soft tissue swelling or a joint effusion. 10,40,41ater stages of septic arthritis may reveal chronic bony changes and calcium deposits. 101][42] Ultrasound may provide assistance in determining the presence of intra-articular effusion and locating the site of optimal aspiration. 10,26,43,44

Synovial Fluid
Synovial fluid is the gold standard for excluding septic arthritis in patients with high clinical suspicion.Results of the aspiration also assist with determining the etiology of joint effusion (Table 3).However, some of these findings may overlap between categories. 8,17,18,45The numbers from this table have been obtained from several meta-analyses and are provided here in one location.
A synovial white blood cell count (sWBC) > 50 x 10 9 /L is concerning for septic arthritis (Table 3). 8,9,17,18][10] While the sWBC values can affect the likelihood of septic arthritis, it is important to consider that the patient's immune status may affect these findings, resulting in low sWBC counts in patients with significant immunocompromised status. 8,9,458,32 Synovial polymorphonuclear cells (sPMN) can also be significantly elevated in cases of septic arthritis. 8,9,15nfortunately, this test does not significantly alter probability of septic arthritis, with a +LR of 2.7 (95% CI [2.1-3.5]) when the sPMN is > 90% and a -LR of 0.34 when the sPMN is < 90%. 8,97,18 Synovial culture is the single most important test and should be ordered on all patients from whom synovial fluid is collected.8,45 To decrease the likelihood of false negative synovial cultures, larger amounts of synovial fluid should be collected and placed in blood culture bottles.18][45][46][47][48][49][50][51][52][53] Synovial protein and glucose do not significantly change the likelihood of septic arthritis. 8,9One study found that a synovial lactic dehydrogenase less than 250 U/L may exclude the diagnosis of septic arthritis, but further studies are needed. 8,53The presence of crystals does not rule out septic arthritis. 8,10,17,18,45,54ynovial lactate has been suggested to have the best diagnostic accuracy of all synovial fluid markers in septic arthritis.6][57] Of note, it is important that the laboratory be able to differentiate D-lactate, produced by bacteria, from L-lactate, produced by humans. 8,57herefore, this may not be feasible at all institutions.

Management
Rapid diagnosis and treatment reduce the risk of significant morbidity and mortality. 10,17,18,58,590][61] Components of management include early recognition and treatment, with 1) joint aspiration, 2) antibiotics, and 3) orthopedic surgery consultation for possible operative management. 10,17,18,58,59ue to the potential for rapid joint destruction, broadspectrum antibiotics are often needed. 17,18,58,59In patients with strong concern for septic arthritis or in those who are critically ill, both Gram-negative and MRSA coverage is recommended with a combination of cefepime or an antipseudomonal betalactam agent and vancomycin, respectively. 17,18,58,59If the patient is allergic to vancomycin, daptomycin, clindamycin, or linezolid may be utilized instead. 17,18,58,59Once the specific organism is determined, antibiotic therapy should be narrowed.There is currently no role for intra-articular antibiotics or intra-articular corticosteroids for these patients in the ED setting. 10,58hile many patients may be managed with antibiotics alone, it is important to involve orthopedic surgery, as some patients may require arthroscopy, serial arthrocentesis, or arthrotomy in addition to the antibiotics. 10,17,18,58,59rthrocentesis removes bacteria and toxins, decompresses the joint space, and improves blood flow, which may improve recovery. 10,17,18,58,59Arthrocentesis is typically repeated on a daily basis until cultures are negative and effusions resolve. 10,17,18,58,59In cases that fail to respond to serial arthrocentesis, soft tissue infections that extend outside of the joint or involvement of the hip joint, surgical drainage is often indicated. 1,58,59[60][61][62][63][64]

Joint Aspiration
Most joint aspirations are within the purview of the emergency physician. 10,58,59While it is traditionally recommended to avoid aspirating through a site with overlying cellulitis, one recent review suggested there was no harm from aspirating through cellulitis, with the only direct definitive contraindication an underlying abscess. 65Additionally, anticoagulation is a relative contraindication, but should be weighed against the much higher risk associated with missing a case of septic arthritis. 66Prosthetic joints should be discussed with orthopedic surgery prior to aspiration. 67If unable to obtain fluid on the initial aspiration, several techniques may be used to increase the likelihood of success.Using a larger gauge needle and a smaller syringe can improve the ability to obtain fluid by generating a greater pressure difference. 68Additionally, compression of the contralateral side of the joint with gentle rotation of the needle while aspirating will be of benefit. 68Finally, ultrasound should be considered for arthrocentesis, as it locates the area with maximal fluid, while avoiding vascular structures and tendons.

Gout
Gout can predispose patients to septic arthritis due to chronic joint damage. 8,10,54,69Patients with a first instance of an erythematous, swollen, painful joint and those with atypical presentations of their usual gout should undergo joint aspiration.Joint fluid in gout traditionally demonstrates uric acid, or calcium pyrophosphate crystals in pseudogout; however, it is important to note that these crystals do not exclude concomitant septic arthritis, as the pathologies may coexist in up to 5% of cases. 54,69Patients with gout and septic Evaluation and Management of Septic Arthritis and its Mimics in the ED Long et al.
arthritis often demonstrate sWBC counts > 50 x 10 9 /L; 54,70 however, up to 10% of patients may demonstrate sWBC < 6 x 10 9 /L. 70Patients with concern for possible septic arthritis should undergo joint aspiration, antibiotics, orthopedic consultation, and admission. 17,18,69,702][73] Patients with either new or chronic joint pain with effusion should undergo aspiration given the high risk of opportunistic infections.

Prosthetic Joint
5][76][77] Unlike native joints, prosthetic joints do not contain cartilage and are not at risk of cartilage destruction. 67,77Acute infections (i.e., < six weeks from operation) should receive urgent antibiotics to preserve the prosthesis, while more chronic infections (i.e., > six weeks from operation) may be treated with less urgency. 67Chronic infection is more common than acute postoperative and acute hematogenous infection in these patients. 78,79][86] Signs and symptoms depend upon the patient's immune response and whether the infection is acute or chronic. 67Acute infections typically present with a new effusion, erythema, and warmth combined with general symptoms of fever and malaise, while chronic infections may present with more subtle signs of pain over time without significant external evidence of infection. 67,76,87Findings may also include an open wound, sinus tract, or abscess. 67,76,88,89][90] Cultures from a draining wound are not recommended due to risk of skin flora contamination. 67,76Diagnostic criteria are shown in Table 4. 67,76 Two positive periprosthetic cultures with phenotypicallyidentified organisms   67,76 Importantly, the specific thresholds for septic arthritis differ compared to native joints.][92] For chronic PJI, sWBC 3 x 10 9 /L and sPMN > 80% are recommended. 74,75,88,89One publication recommended joint aspiration for a CRP > 100 mg/L for acute infection. 67evision surgery and antibiotics are usually required.However, compared with native joint infections, these are typically not needed emergently. 67,76If patients present with fever and an acute onset of symptoms, blood cultures should be obtained and antibiotics administered in the ED. 67,76therwise, antibiotics may be withheld until the case is discussed with the orthopedic surgeon. 67,76

Hemophilia
4][95][96] Patients with hemophilia who have joint pain, swelling, or erythema should be asked about prior hemarthroses, factor levels, prophylactic medications, and recent factor administration.In most patients, joint aspiration should be avoided in the setting of hemarthrosis. 97,984][95][96] Aspiration of hemarthrosis may improve pain and rehabilitation in patients with rapid intra-articular accumulation of blood, although this is controversial. 97,98efore conducting aspiration of suspected hemarthrosis,

Long et al.
Evaluation and Management of Septic Arthritis and its Mimics in the ED emergency physicians should discuss the aspiration with hematology and orthopedics, specifically addressing possible factor replacement prior to joint aspiration. 97,98mics A significant number of conditions may mimic the presentation of septic arthritis, creating difficulty in diagnosis.Knowledge of these conditions and their presentation, diagnosis, and management may improve patient outcomes.Table 5 demonstrates these conditions, and Appendix 1 lists these mimics with evaluation and management recommendations.

CONCLUSION
Septic arthritis is a potentially deadly condition that unfortunately does not always present classically.The red, hot, swollen joint mandates consideration of septic arthritis.No physical examination finding can rule out the condition, and serum blood tests should not be used to exclude septic arthritis.Diagnostic aspiration is required, with the sample sent for synovial WBC, Gram stain, culture, and lactate.Synovial lactate and culture are the best laboratory tests, as some patients can present with normal synovial WBC and Gram stain.Management requires orthopedic surgery consultation and antibiotics.There are a significant number of mimics of septic arthritis, including abscess, cellulitis, gout, rheumatoid arthritis, osteomyelitis, malignancy, Lyme disease, and avascular necrosis.A focused history and examination, along with dedicated diagnostic evaluation, can assist in differentiating these conditions.

OrA
sinus tract communicating with the joint Or Three of the following minor criteria: Elevated CRP and ESR Elevated sWBC or positive leukocyte esterase strip Elevated synovial neutrophil percentage Positive histologic analysis of periprosthetic tissue A single positive culture result CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; sWBC, synovial white blood cell count.

Table 3 .
Risk factors associated with increased risk of joint destruction include age > 65 years, diabetes, and beta-hemolytic streptococci infection, while risk factors for mortality include age > 65 years, confusion at time of initial presentation, Western Journal of Emergency Medicine Long et al.Evaluation and Management of Septic Arthritis and its Mimics in the ED PMNs, polymorphonuclear neutrophil; sWBC, synovial white blood cell count; sPMN, synovial polymorphonuclear cell count; sLactate, synovial lactate; CI, confidence interval; +LR, positive likelihood ratio; -LR, negative likelihood ratio; L, liter.*Unable to pool results to obtain accurate 95% confidence intervals.Categories of synovial fluid findings in monoarticular arthritis.

Table 4 .
Musculoskeletal Infection Society definition of periprosthetic joint infection.