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Three Part Question

In [adults presenting to the ED with an acute hot joint] is [WBC of the joint aspirate ] sufficiently specific and sensitive [to rule in/out septic arthritis]

Clinical Scenario

A 20 year old university student presents to the ED with two day history of a hot, swollen joint. She reports no prior knee swelling and no recent trauma or knee surgery, illegal drug use, rash, uvetis or risky sexual behavior. On examination, she is afebrile and has a left knee effusion. Her WBC, ESR and CRP are all raised. The joint aspirate reports an elevated WBC and negative gram stain and culture. You wonder what value knowing the WBC and differential of the joint aspirate will give you in making a diagnosis and ruling out SA?

Search Strategy

Multifile search using OVID – Medline (1950-2008), Embase (1980-2008), CINAL (1982-2008), Cochrane ({[ exp. Infectious Arthritis OR hot joint.mp OR septic joint.mp OR septic arthritis.mp] AND [ exp. Blood Cell Count, exp neutrophils, white cell count$.mp OR white blood cell count$.mp] AND [ exp Synovial fluid OR aspirate$.mp OR synovial fluid$.mp]}) Limited to Humans, English Language and Adults

Search Outcome

The following number of articles were identified from each of the databases: Medline 51 citations, Embase 57 citations, CINAL 5 citations, Cochrane 2 citations. Duplicates and irrelevant titles removed from 115 articles leaving a total of 5 relevant articles.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Margaretten ME. et al, 2007, USA	Fourteen studies involving 6242 patients, of whom 653 diagnosed with SA and met all respective inclusion criteria.	Systematic Review (Level 1)	Summary of sensitivities and LR of raised WBC in joint aspirate.Percentage of polymorph nuclear cells from arthrocentesis from four studies	LR increases as synovial fluid WBC count increases<25000/uL:LR, (0.32;95% CI, 0.23-0.43 >25000/uL;LR( 2.9;95% CI, 2.5-3.4 >50000/UlLR (7.7;95%CI, 5.7-11.0>100000/uLLR (28.0;95% CI,12.0-66.0) On the same sample polymorph nuclear cell count of 90% (LR of 3.4;95%CI, 2.8-4.2) <90% (LR 0.34;95%CI 0.25-0.47)	Value at which statistical tests, demographics and co morbidities in each individual study were not noted.
Li SF et al, 2004, USA	73 patients with confirmed positive arthrocentesis culture or operative findings	Retrospective consecutive case series(Level 3)	WBC/mm3 in joint aspirate	Sensitivity(0.64;95%CI,0.51-0.76)Mean, median, (range)127,000, 66,160,(168->1million)	Case series. Small sample. Unable to determine specificity.
McCutchan HJ et al, 1990, USA	41 patients with clinical presentation of SA where 92% of patients where considered immunocompromised. (neoplasia, steroid use of IVDU)	Case Series (Level 3)	Raised WBC /mm3 in joint aspirate( of three patient groups )	Mean, median (range) 46,500, 28,000(5,200-156,000 cells/mm3)	Case series. Small sample.
Li SF et al, 2007, USA	156 patients who had undergone arthrocentesis, 16 were confirmed SA by culture or operative findings	Retrospective Cohort study (Level 2)	Raised WBC/mm3 of joint aspirate	Sensitivity 0.50 Specificity 0.88. LR(+)4.0 LR(-)0.57 ROC –AUC (0.69; 95%CI, 0.57-0.80) Cutoff of jWBC =17,500 maximized sensitivity (83%) and specificity (67%)	Small sample. No sample size calculation. No gold standard. First ROC to be reported on this test. Results may not be generalisable given the variations in laboratories and patient populations.
Daniel et al, 2007, USA	49 culture positive synovial fluid aspirates in an ED in an urban tertiary care center	Case Series (Level 3)	Raised WBC/mm3 of joint aspirate	19/49 (39%) patients had a synovial WBC< 50 000/mm (95% CI, 25%-52%) Sensitivity of the 50 000 synovial WBC/mm3 cutoff (0.61; 95% CI, 0.48-0.75).	Case Series. Unable to calculate specificity. Imperfect gold standard* Narrow definition for SA.

Comment(s)

From the evidence, sensitivity and specificity can neither rule out or rule in SA (Margaretten, Li 2004). The value at which these statistical tests have been based is not always noted and comparable among different subsets of patients studied. Although it seems that the likelihood ratio becomes more valuable diagnostically as the WBC increases, and in particular the polymorphonuclear cells, a cutoff value is what would be most use. The best evidence that involves receiver operator characteristic (ROC) analysis suggests that a value between 1500 and 2000 cells/mm3, namely polymorphonuclear cells, seems to be associated with maximum sensitivity (83%) and specificity (60–67%). This still may not be applicable to all patient groups, ie, immunocompromised (McCutchan). According to the area under the curve (AUC) ROC, WBC of the joint aspirate (jWBC) was considered fair, good and the best diagnostic test, ahead of WBC and ESR (Li, 2007). The combined sensitivity of jWBC, ESR and WBC is 100% despite their low combined specificity (0.24) (Li, 2004, 2007). If there is no elevation of these three tests, this may be sufficient to rule out SA when the clinical picture is uncomplicated; however, along with the other ancillary tests, WBC of the joint aspirate should be regarded as an adjunct to the diagnosis of SA (Li, 2007).

Clinical Bottom Line

The WCC alone of the joint aspirate does not have the sensitivity or specificity to rule out or in SA. *Imperfect Gold Standard –gram stain (sensitivity 29-50%) and culture (sensitive-82%) [Margaretten] *Imperfect Gold Standard –gram stain (sensitivity 29-50%) and culture (sensitive-82%)

References

1. Soderquist B. Bacterial or Crystal –associated Arthritis? Discriminating Ability of Serum Inflammatory Markers. Scandinavian Journal of Infectious Diseases. 1998;30:591-596.
2. Kortekangas P. Synovial fluid in bacterial arthritis vs. reactive arthritis and rheumatoid arthritis in the adult knee. Scandinavian Journal of Rheumatology. 1992;21:283-288.
3. Krey PR. Synovial fluid leukocytosis :a study of extremes. American Journal of Medicine. 1979;67:436-442 .
4. Shmerling RH. Synovial fluid tests: what should be ordered? JAMA 1999;26:1009-1014.
5. Margaretten ME. Does the Adult Patient Have Septic Arthritis? JAMA 2007;297(13):1478-1488.
6. Li SF. Laboratory Tests in Adults with Monoarticular Arthritis: Can They Rule Out a Septic Joint? Emergency Journal of Medicine. 2004;11(3):276-280.
7. Mc Cutchan HJ. Synovial leukocytosis in infectious arthritis. Clinical Orthopaedics and Related Research . 1990;(257):226-230.
8. Li SF. Diagnostic utility of laboratory tests in septic arthritis. Emergency Journal of Medicine. 2007; 24:75-77.
9. Daniel C. How sensitive is the synovial fluid white blood cell count in diagnosing septic arthritis? American Journal of Emergency Medicine. 2007; 25:749-752.