Publish in this journal
Journal Information
Vol. 12. Issue 2.
Pages 114-115 (March - April 2016)
Vol. 12. Issue 2.
Pages 114-115 (March - April 2016)
Letter to the Editor
DOI: 10.1016/j.reumae.2015.05.007
Full text access
False Negatives of Synovial Fluid in Septic Arthritis
Falsos negativos del líquido sinovial en la artritis séptica
Joaquín Anino-Fernández
Corresponding author

Corresponding author.
, Marco Aurelio Ramírez-Huaranga, María Dolores Mínguez-Sanchez
Servicio de Reumatología, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain
Article information
Full Text
Download PDF
Full Text
To the Editor,

The analysis of the synovial fluid (SF) is a fundamental tool in the study of monoarthritis, as it reflects changes in the synovial membrane and underlying articular cartilage. The findings in the SF are essential in infectious and crystal arthritis.1,2

To date, SF culture continues to be the gold standard for the microbiological diagnosis of septic arthritis.3,4 The pathogen most frequently isolated in septic joint processes is Staphylococcus aureus (50%–60%), followed by streptococci, found in up to 20% of the cases. Gram-negative bacilli are the cause in only 5%–10% of the cases of septic arthritis.5

We report the case of a patient who experienced an episode of septic arthritis in which the SF study showed no evidence of inflammation.

The patient was a 49-year-old man with no toxic habits. He had a history of untreated Rendu–Osler–Weber disease. He presented with monoarthritis in the left knee that had developed several days earlier, without fever or any other accompanying symptoms.

On physical examination, he was afebrile. The only significant finding was joint effusion with functional impairment and inflammation in left knee. He underwent arthrocentesis, which yielded 10mL of SF with inflammatory features: 12,500leukocytes/mm3, predominance of polymorphonuclear cells (95%) and glucose level of 82mg/dL. No crystals were observed in a microscopic study. Gram stain was negative. Laboratory tests revealed no evidence of leukocytosis (6100×109leukocytes, 62% neutrophils and 27% lymphocytes), but showed elevated acute phase reactants (C-reactive protein 1.4mg/dL; fibrinogen: 600mg/dL). The study was completed with radiographies of the knees, which revealed conserved alignment and mineralization, and no periosteal reaction or erosions. While waiting for the results of the microbiological study, we started treatment with nonsteroidal anti-inflammatory drugs (NSAID). Five days after this episode, he presented with more intense pain, without fever or any other symptoms. The physical examination revealed joint effusion and inflammation in left knee, with no other significant changes. Arthrocentesis was repeated, and yielded 38mL of SF with no inflammatory features: 1960leukocytes/mm3, 35% polymorphonuclear cells and glucose level of 84mg/dL. However, methicillin-sensitive Staphylococcus aureus was identified in 2 separate SF cultures. Urine sediment was normal and blood and urine cultures were negative. The study was completed with bone scintigraphy and labeled white blood cell scan—both of which were positive for septic arthritis—and chest radiography and echocardiography, which ruled out lung and cardiac involvement. Laboratory tests revealed positivity for HLA-B27. Antibiotic therapy was begun with ceftriaxone 2g every 24h and cloxacillin 2g every 6h. Emergency surgical joint lavage with saline solution was carried out. Subsequent cultures were negative. No cancer cells were found in the pathological study. The patient remained in the hospital until he had completed a 15-day intravenous treatment. He experienced clinical improvement, remission of the infectious process and recovery of knee function.

Although the study of the SF is fundamental and of great help in monoarthritis, in certain specific situations (immunosuppression, previous antibiotic use, and chronic or very acute conditions), the results do not clearly reveal what is taking place at the level of the joints. Thus, the microbiological study continues to be the gold standard for the diagnosis of septic arthritis.3,4 In these situations, tests like bone scintigraphy or positron emission tomography (PET) lend great support to the diagnosis. Moreover, we found that the Gram stain currently used for SF is of no value in the diagnosis of septic arthritis, as the rate of false negatives ranges from 25% to 50%, according to the literature,6,7 and was as high as 78% in a retrospective study conducted by the Manchester Royal Infirmary.8 This makes the technique a tool of little use when the clinical picture constitutes an orthopedic emergency with significant morbidity and a mortality of up to 11%.3,4,9 Investigation is underway to find alternative diagnostic techniques, such as the use of lithium heparin containers for SF sample collection to prevent coagulation. These modification are being assessed in order to quantify the extent to which they will reduce false negatives with Gram staining in SF.7–10

Finally, we can conclude that early diagnosis is essential to limit the morbidity and mortality. A delay in the treatment of septic arthritis can lead to the rapid destruction of the articular cartilage.3–8 Thus, given the high rate of false negatives with Gram staining, it is necessary either to improve the diagnostic techniques or dissociate SF from the process taking place at the level of the joint.

Aparato locomotor: exploraciones complementarias en Atención Primaria.
Sociedad Española de Medicina de Familia y Comunitaria, (2007),
Freire González M. Pruebas de laboratorio en Reumatología. Guía fisterra. Available from: http://www.fisteraaocom [accessed 04.05.12].
G. Coakley, C. Mathew, M. Field, A. Jones, G. Kingsley, D. Walker, British Society for Rheumatology Standards, Guidelines and Audit Working Group, et al.
BSR & BHPR, BOA, RCGP and BSAC guidelines for management of the hot swollen joint adults.
Rheumatology (Oxford), 45 (2006), pp. 1039-1041
C.J. Kaandorp, P. Krijnen, H.J. Moens, J.D. Habbema, D. van Schaardenburg.
The outcome of bacterial arthritis a prospective community-based study.
C.R. Carpenter, I.D. Schuur, W.W. Everett, J.M. Pìnes.
Evidence-based diagnosis: adult septic arthritis.
Acad Emerg Med, 18 (2011), pp. 781-796
R.H. Shemerling.
Synovial fluid analysis. A critical reappraisal.
Rheum Dis Clin North Am, 20 (1994), pp. 503-512
D.L. Goldenberg.
Septic arthritis.
P. Stirding, R. Faroung, S. Amanat, A. Ahmed, M. Armstrong, P. Sharma, et al.
False negative rate of Gram-stain microscopy for diagnosis of septic arthritic: Suggestions for improvement.
Int J Microbiol, 2014 (2014),
P. Vostrel, L. Legout, P. Hoffmeyer.
Septhic arthritis (non-gonococcal) of the adult: practical aspects.
Rev Med Suisse, 2 (2006), pp. 2924-2930
J. Denton.
Synovial fluid analysis in the diagnosis of joint disease.
Diagn Histopatol, 18 (2012), pp. 159-168

Please cite this article as: Anino-Fernández J, Ramírez-Huaranga MA, Mínguez-Sanchez MD. Falsos negativos del líquido sinovial en la artritis séptica. Reumatol Clin. 2016;12:114–115.

Copyright © 2015. Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología
Reumatología Clínica (English Edition)

Subscribe to our newsletter

Article options
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?