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Do Negative Serum Biomarkers Rule Out Septic Arthritis?

Three Part Question

In [adult patients presenting with an acute hot joint] do [negative serum biomarkers] compared with [clinical assessment, synovial fluid microscopy and culture] rule out [septic arthritis]?

Clinical Scenario

A 48-year-old male with a history of type 2 diabetes
presents to the emergency department with left knee pain. On examination, his left knee is erythematous with an effusion and tender to palpation. He is very
painful with both passive and active range of motion. You would like to rule out a septic joint in the most reliable and least invasive way, and consider which laboratory tests to order.

Search Strategy

Medline 1966-04/24 using PubMed, Embase, Cochrane Library (2024)

[(serum markers OR biomarkers OR erythrocyte sedimentation rate OR procalcitonin OR c-reactive protein) AND (exp septic arthritis OR exp septic joint)] LIMIT to adults and English language.

Search Outcome

189 total articles were found, one meta-analysis was identified as both relevant and of sufficient quality for inclusion.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Dey M, et al.
May 2023
United Kingdom
Patients presented with an acutely swollen hot native joint and were undergoing diagnostic tests, in either the synovial fluid, the serum or both, to aid diagnosis and management of the acute hot joint.Meta-analysisC-reactive protein greater than 10 mg/L Sensitivity, 0.87 to 0.91 Heterogeneity of study design, outcomes and thresholds. Conclusions dependent on quality of individual articles referenced.
Erythrocyte sedimentation rate greater than 50 mm/hSensitivity, 0.42 to 0.82
White blood cell greater than 10 × 109/L Sensitivity, 0.50 to 0.75
Procalcitonin greater than 0.3 ng/mLSensitivity, 0.09 to 0.73


Regardless of the threshold selected, no study demonstrated an acceptable sensitivity or overall diagnostic accuracy to rule out septic arthritis. No cutoff for WBC, ESR or C-reactive protein (CRP) significantly increased or decreased the posttest probability of septic arthritis. Tumor necrosis factor, and various cytokines including interleukin were also generally specific with very poor sensitivity.

Clinical Bottom Line

No single biomarker can diagnose or exclude septic arthritis alone.


  1. Dey M, Al-Attar M, Peruffo L, Coope A, Zhao SS, Duffield S, Goodson N. Assessment and diagnosis of the acute hot joint: a systematic review and meta-analysis. Rheumatology (Oxford) 2023 May 2;62(5):1740-1756