Laboratory Tests in Adults with Monoarticular Arthritis: Can They Rule Out a Septic Joint?

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1 276 Li et al. d LABORATORY TESTS FOR SEPTIC JOINT Laboratory Tests in Adults with Monoarticular Arthritis: Can They Rule Out a Septic Joint? Abstract It is difficult to differentiate septic arthritis from other causes of monoarticular arthritis solely with a history and physical examination. The clinician must rely on ancillary tests to make a diagnosis, such as the white blood cell count of peripheral blood (WBC), the erythrocyte sedimentation rate (ESR), and the white blood cell count of the joint fluid ( jwbc) obtained from arthrocentesis. Although it is known that septic arthritis is associated with abnormalities in these tests, the majority of the data are based on studies in the pediatric population. In addition, although several emergency medicine texts indicate that a jwbc greater than 50,000 cells/mm 3 is positive, it is known that septic arthritis can occur in patients with low jwbcs. Objectives: To determine whether specific ancillary tests have sufficiently high sensitivities to rule out septic arthritis in adults. Methods: This was a retrospective consecutive case series of patients from an urban emergency department (ED). Patients at least 18 years old who had septic arthritis Siu Fai Li, MD, Jessica Henderson, MD, Eitan Dickman, MD, Robert Darzynkiewicz, MD confirmed by positive arthrocentesis culture or operative findings were included in the study. WBC greater than 11,000 cells/mm 3, ESR greater than 30 mm/hr, and jwbc greater than 50,000 cells/mm 3 were considered elevated. Results: Seventy-three patients met the inclusion criteria. The sensitivities of an elevated WBC, ESR, or jwbc in adults who had septic arthritis were 48%, 96%, and 64%, respectively. There were broad ranges of WBC, ESR, or jwbc among the patients. More than one third of adult patients with septic arthritis had jwbcs less than 50,000 cells/mm 3. All patients had an abnormality in at least one of these tests. Conclusions: The WBC, ESR, and jwbc are extremely variable in adults with septic arthritis. Laboratory tests do not rule out septic arthritis with accuracy. Key words: septic arthritis; sensitivity; erythrocyte sedimentation rate; arthrocentesis; leukocytosis; diagnosis. ACADEMIC EMER- GENCY MEDICINE 2004; 11: Septic arthritis is perhaps the most serious cause of monoarticular arthritis in adults. As such, emergency physicians (EPs) must primarily rule out septic arthritis when faced with an inflamed joint. It is rarely possible to make a definitive diagnosis based on the history and physical examination, and the clinician must rely on ancillary tests, such as the white blood cell count of peripheral blood (WBC), the erythrocyte sedimentation rate (ESR), and direct arthrocentesis of the affected joint. In particular, the white blood cell count of the joint fluid (jwbc) is often used to help differentiate septic arthritis from other entities. Although it is known that septic arthritis is associated with elevations in WBC, ESR, and jwbc, the vast majority of the studies involve the pediatric population, 1 15 with few studies exclusively in adults In addition, although several emergency medicine From the Department of Emergency Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY (SFL, JH, ED, RD). Received May 1, 2003; revision received August 22, 2003; accepted September 18, Address for correspondence and reprints: Siu Fai Li, MD, Department of Emergency Medicine, Jacobi Medical Center, 1400 Pelham Parkway South, Bronx, NY Fax ; souffle@banet.net. doi: /j.aem textbooks indicate that a jwbc greater than 50,000 cells/mm 3 is likely to be positive, the number at which a jwbc is considered negative for septic arthritis varies from 2,000 to 10,000 cells/mm 3 in different texts There are several reports of septic arthritis in patients with low jwbcs, 17 19,25 30 so it is not clear if there is any jwbc that would rule out a septic joint. We conducted a retrospective case series study to determine the sensitivities of elevated WBC, ESR, and jwbc in adult patients with septic arthritis to determine whether a septic joint can be ruled out by any (or a combination of) these ancillary tests. METHODS Study Design. This was a retrospective study of cases of septic arthritis in adults at an urban teaching hospital. The committee on clinical investigations at our institution approved the study. Study Setting and Population. Patients were included in the study if they were 18 years of age and older and the diagnosis of septic arthritis was confirmed by a positive arthrocentesis culture or operative findings, such as the presence of grossly purulent material. Patients 65 years of age and older were considered elders.

2 ACAD EMERG MED d March 2004, Vol. 11, No. 3 d Figure 1. Derivation of the study sample. Study Protocol. The hospital medical database was queried for adult patients who were discharged with a diagnosis of septic arthritis from 1996 to Demographic (age, gender, and race), clinical (e.g., medical history), and laboratory (e.g., WBC and ESR) data were obtained from the hospital s patient information computer database. In our laboratory, the normal range for WBC is 3,500 11,000 cells/mm 3 and 5 30 mm/hr for ESR. A jwbc greater than 50,000 cells/mm 3 was considered high. In patients who underwent multiple arthrocenteses, the results of the initial arthrocentesis were used in this study. Data Analysis. Sensitivities of WBC, ESR, and jwbc were determined by using simple proportions and 95% confidence intervals (95% CIs). By using the presence of leukocytosis as the primary outcome, it was estimated that 72 patients were needed for an expected occurrence of 75%, to detect a 10% difference, with a two-tailed alpha of RESULTS The database identified 92 patients, of whom 73 met inclusion criteria (Figure 1). Sixty-one patients had a positive arthrocentesis culture. The remaining 12 patients who did not have positive arthrocentesis cultures had frank pus at arthroscopy. Five of the 12 patients had positive cultures from synovial fluid obtained at operation. TABLE 1. Demographics of the Study Set Age (y) (mean 6 SD) Gender (% male) 71 Elder (%) (age [65 yr) 19 Diabetes (%) 21 HIV (%) 13 Mortality (%) 6.5 SD = standard deviation. The demographics of the patients are summarized in Table 1. The most common joint involved was the knee, followed by the shoulder (Table 2). The most common pathogen was Staphylococcus aureus, followed by group B streptococcus (Table 3). Thirty-six percent of all patients were either diabetic (22%) or HIV-positive (14%). Five patients (7%) died from complications related to the joint infection. Mortality was strongly associated with elder patients (relative risk [RR] = 17; 95% CI = 2.0 to 139) but not with patients with diabetes or HIV (Table 4). Of the 73 patients, an ESR was obtained for 59 patients, 70 underwent arthrocentesis, and a peripheral WBC was obtained for all patients. Sixty-one of the patients who had arthrocentesis had synovial fluid cell count analyses; the remaining nine patients had synovial fluid cultures only. The means 6 standard deviations of the WBC, ESR, and jwbc in adults with septic arthritis were TABLE 2. Location of Affected Joints* Knee 43 Shoulder 11 Wrist 6 Hip 6 Ankle 5 Elbow 4 Other 3 *Five patients had multiple joint involvement. TABLE 3. Results of Microbiologic Cultures Staphylococcus aureus 42 Group B streptococcus 6 Streptococcus pneumoniae 3 Group A streptococcus 2 Group G streptococcus 2 1 each of Bacillus species, Escherichia coli, Neisseria gonorrhoeae, Haemophilus influenzae, Klebsiella pneumoniae, Lactobacillus, Pseudomonas aeruginosa, and Streptococcus viridans.

3 278 Li et al. d LABORATORY TESTS FOR SEPTIC JOINT TABLE 4. Mortality Risk of Subgroups of Patients with Septic Arthritis Elders ? 1 58 RR ¼ 17 (95% CI ¼ 2.0 to 139) Diabetes ? 3 54 RR ¼ 2.4 (95% CI ¼ 0.43 to 13) HIV + 1 9? 4 59 RR ¼ 1.6 (95% CI ¼ 0.2 to 13) RR ¼ relative risk; CI ¼ confidence interval. 12, ,900 cells/mm 3, mm/hr, and 114, ,000 cells/mm 3, respectively. There were wide ranges of values for each of the laboratory tests (Figures 2 4). The sensitivities of elevations in WBC, ESR, and jwbc for adult septic arthritis were 48%, 96%, and 64%, respectively (Table 5). All of the patients had an abnormality in at least one of these tests. DISCUSSION Septic arthritis remains a difficult diagnosis even with the use of blood tests and arthrocentesis. In our study, the sensitivities of the WBC and jwbc were poor, missing approximately one half and one third of cases, respectively. The ESR was the only ancillary test that showed a high sensitivity in patients with septic arthritis. However, a substantial portion of our patients (7%) had relatively low ESRs (\40 mm/hr), Figure 3. Erythrocyte sedimentation rate (ESR) in adults with septic arthritis. and two patients (3%) had a normal ESR (\30 mm/ hr). Furthermore, the role of the ESR may be limited because of its lack of specificity for septic arthritis. 7,8,13,14,31,32 In our patient sample, there was a large proportion (36%) of patients with septic arthritis who had jwbc less than 50,000 cells/mm 3. The range of jwbc was quite broad, with a substantial number of patients (6 of 61 [10%]) who had counts less than 10,000 cells/ mm 3 ; the lowest jwbc was 168 cells/mm 3. There are other reported cases of septic arthritis in the literature with similarly low jwbc ,25 30 Although these data are consistent with some earlier studies, 17,18,25,29 they run contrary to the common notion that septic arthritis is infrequently seen in patients with jwbc less than 50,000 cells/mm 3. Past studies have reported variable sensitivities of these ancillary tests for septic arthritis. The sensitivity of an elevated WBC ranges from 19% to 77%, 2,4 8,13 19,21,25 27,33 the sensitivity of an elevated ESR ranges from 71% to 94%, 2 8,14,15,17 21,30,33 35 and the sensitivity of a jwbc greater than 50,000 cells/mm 3 ranges from 0% to 92%. 1,3,17 19,21,25 30,33,36,37 Much of the literature consists of case series studies like ours, often Figure 2. White blood cell (WBC) count in adults with septic arthritis.

4 ACAD EMERG MED d March 2004, Vol. 11, No. 3 d Figure 4. White blood cell count of the joint fluid ( jwbc) in adults with septic arthritis. *Eight patients with jwbc greater than 250,000 cells/mm 3. with variable values for normal WBC, ESR, and jwbc. The studies also have heterogeneous control groups, making it difficult, if not impossible, to perform an adequate meta-analysis. LIMITATIONS Our study is limited by several factors. First, our study is designed as a case series, so it was not possible to determine the specificity (and overall diagnostic accuracy) of the ancillary tests. However, the sensitivities allow us to comment on the ability of these tests to rule out septic arthritis, but not the ability of these tests to rule in septic arthritis. Second, our inclusion criteria were narrowly defined, and we may have excluded some patients who likely had septic arthritis, such as those who had jwbcs between 50,000 and 100,000 cells/mm 3, who had positive blood cultures, and who responded to antibiotics. Third, although the combination of all three tests was 100% sensitive in detecting septic arthritis in adults, the 95% CI of the sensitivity was only 95 to 100 because of the sample size of our study. Thus, our findings must be confirmed in a larger cohort. CONCLUSIONS TABLE 5. Sensitivities of Laboratory Indicators in Adult Septic Arthritis Sensitivity (95% CI) Mean Median Range WBC 0.48 (0.36, 0.60) 12,800 10,800 3,500 31,000 ESR 0.96 (0.88,1.0) jwbc 0.64 (0.51, 0.76) 127,000 66, [1 million All (0.95, 1.0) WBC = white blood cell count; ESR = erythrocyte sedimentation rate; jwbc = WBC of the joint fluid. It may not be possible to accurately rule out septic arthritis in adults even with the use of ancillary blood tests and arthrocentesis. The most prudent plan for patients with suspected septic arthritis might be a conservative approach with either hospital admission or extremely close follow-up and possibly repeat arthrocentesis. References 1. Kunnamo I, Pelkonen P. Routine analysis of synovial fluid cells is of value in the differential diagnosis of arthritis in children. J Rheumatol. 1986; 13: Unkila-Kallio L, Kallio MJT, Peltola H. The usefulness of C-reactive protein levels in the identification of concurrent septic arthritis in children who have acute hematogenous osteomyelitis. J Bone Joint Surg Am. 1994; 76: Culp RW, Eichenfield AH, Davidson RS. Lyme arthritis in children. J Bone Joint Surg Am. 1987; 69: Morrey BF, Bianco AJ, Rhodes KH. Septic arthritis in children. Orthop Clin North Am. 1975; 6: Rotbart HA, Glode MP. Haemophilus influenza type b septic arthritis in children: report of 23 cases. Pediatrics. 1985; 75: Kallio MJT, Unkila-Kallio L, Aalto K. Serum C-reactive protein, erythrocyte sedimentation rate and white blood cell count in septic arthritis of children. Pediatr Infect Dis J. 1997; 16: Kunnamo I, Kallio P, Pelkonen P. Clinical signs and laboratory tests in the differential diagnosis of arthritis in children. Am J Dis Child. 1987; 141: DelBaccaro MA, Champoux AN, Bockers T. Septic arthritis versus transient synovitis of the hip: the value of screening laboratory tests. Ann Emerg Med. 1992; 21: Todd JK. Childhood infections. Diagnostic value of peripheral white blood cell and differential cell counts. Am J Dis Child. 1974; 127: Baldassare AR, Chang F, Zuckner J. Markedly raised synovial fluid leucocyte counts not associated with infectious arthritis in children. Ann Rheum Dis. 1978; 37: Yamanaka L, Herbert ME. Myth: an elevated leukocyte count distinguishes septic arthritis from less serious causes of hip pain. West J Med. 2001; 175: Kocher MS, Zurakowski D, Kasser JR. Differentiating between septic arthritis and transient synovitis of the hip in children: an evidence-based clinical prediction algorithm. J Bone Joint Surg Am. 1999; 81: Eich GF, Superti-Furga A, Umbricht FS. The painful hip: evaluation of criteria for clinical decision-making. Eur J Pediatr. 1999; 158: Molteni RA. The differential diagnosis of benign and septic joint disease in children. Clinical, radiologic, laboratory, and joint fluid analysis, based on 37 children with septic arthritis and 97 with benign aseptic arthritis. Clin Pediatr. 1978; 17: Klein DM, Barbera C, Gray ST. Sensitivity of objective parameters in the diagnosis of pediatric septic hips. Clin Orthop. 1997; 338:153 9.

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