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Is there a role for serum procalcitonin in the differentiation between septic and non-septic arthritis?

Three Part Question

In [a patient with a swollen and tender joint] does [serum procalcitonin level] assist in [the differentiation between septic and nonseptic arthritis]?

Clinical Scenario

A 60-year-old man comes to the emergency room with his right knee swollen and has experienced pain for two days. He has concomitant fever and history of gouty arthritis. Laboratory studies do not demonstrate specific findings except a slightly higher serum level of uric acid. You wonder whether or not serum procalcitonin could be helpful in the differentiation between septic and nonseptic arthritis.

Search Strategy

Medline 1950 to August 2008, Embase 1980 to August 2008, Cinahl 1982 to August 2008, and Cochrane Library 2008
(exp Arthritis or arthritis.mp) AND (exp procalcitonin or procalcitonin.mp) LIMIT to human AND English

Search Outcome

Medline: 15 papers, Embase: 24 papers, Cinahl: 1 paper. 5 were considered to be original research of high quality and relevant to the topic of interest (Table 1). No additional relevant citations were found in the Cochrane Library.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Söderquisto et al
1998
Sweden
54 bacterial arthritis patients (median age 72 years old) and 34 crystal-associated arthritis (median age 78 years old)Retrospective Cohort studyProcalcitonin (PCT) levelsFor PCT level >0.5 ng/ml, bacterial arthritis (n=47) was predicted with sensitivity 42%, specificity 67%, PPV 67%, NPV 42%, LR+ 1.3Small number of patients. Retrospective design. Only two types of arthritis studied. Only hospitalized patients included. Not an ED setting. PCT not evaluated in every patient.
Martinot et al
2005
France
42 patients hospitalized for acute arthritis, including 11 bacteria arthritis patients (mean age 68.4 years), 18 rheumatoid arthritis patients (mean age 62.7 years) and 13 crystal-induced arthritis patients (mean age 68.8 years)Cohort studyPCT levelsFor PCT level >0.3 ng/ml, septic arthritis (n=11) was predicted with sensitivity 73%, specificity 94%, PPV 80%, NPV 85%, LR+ 11.3Small number of patients. Only hospitalized patients included. Not an ED setting.
Butbul-Aviel et al
2005
Israel
44 patients (aged 2 weeks to 19 years) with fever and symptoms consistent with acute arthritis or osteomyelitisCohort studyPCT levelsFor PCT level >0.5 ng/ml, septic arthritis (n=11) was predicted with sensitivity 27%, specificity 79%, PPV 30%, NPV 76%, LR+ 1.3Small number of patients. Synovial fluid aspiration not performed in every septic arthritis patient.
Fottner et al
2008
Germany
33 patients with symptoms consistent with acute arthritisCohort studyPCT levelsFor PCT level >0.5 ng/ml, acute septic arthritis (n=15) was predicted with sensitivity 53%, specificity 100%, PPV 100%, NPV 72%. For PCT level >0.2 ng/ml, acute septic arthritis (n=15) was predicted with sensitivity 100%, specificity 94%, PPV 94%, NPV 100%, LR+ 18 Small number of patients. The patient characteristics not available.
Hügle et al
2008
Switzerland
42 hospitalized patients (age > 16 years old) with mono- or oligoarthritisCohort studyPCT levelsFor PCT level >0.25 ng/ml, septic arthritis (n=14) was predicted with sensitivity 93%, 75% PPV, 65% NPV, LR+ 3.7Small number of patients. Only hospitalized patients included. Not an ED setting. Too many concurrent infections in the study population.

Comment(s)

Early differentiation of septic and nonseptic arthritis remains a challenging task for emergency physicians. Clinical symptoms and traditional serum inflammatory markers are of limited use. Arthrocentesis with synovial gram stain and culture remains the gold standard for septic arthritis. However, the sensitivity of gram stain is only 50-70% and synovial culture aids little in initial clinical decision making. Procalcitonin is promoted as an ideal marker for bacterial infections, such as respiratory tract infections, meningitis, and acute infectious endocarditis. Therefore, we briefly review the role of procalcitonin in septic arthritis in the hope of finding a rapid and reliable marker to solve this clinical dilemma. The studies in Table 1 demonstrate that the use of procalcitonin may be helpful in the differentiation between septic and nonseptic arthritis. All studies suffer from a small number of patients and the results are not in complete accord. Three studies included only hospitalized patients and therefore were not an Emergency Department setting. One study did not perform synovial fluid aspiration in every patient and use clinical findings and positive bone scan as the gold standard. In general, the specificity is moderately high. Reducing the diagnostic serum level of PCT to 0.25-0.3 ng/mL may modestly increase sensitivity for septic arthritis. In this way, it would be easier for emergency physicians to make decisions for safe discharge of patients with suspicious septic arthritis. It is concluded that the measurement of serum levels of procalcitonin appears to be a promising marker in the differentiation of septic and non-septic arthritis.

Clinical Bottom Line

There is insufficient evidence to support the routine use of serum procalcitonin in the differentiation of septic and nonseptic arthritis. However, the specificity is moderately high and current studies show some promise. Further research is needed to answer this question.

References

  1. Soderquist B, Jones I, Fredlund H, et al. Bacterial or crystal-associated arthritis? Discriminating ability of serum inflammatory markers. Scand J Infect Dis 1998; 30(6):591-6.
  2. Martinot M, Sordet C, Soubrier M, et al. Diagnostic value of serum and synovial procalcitonin in acute arthritis: a prospective study of 42 patients. Clin Exp Rheumatol 2005;23(3):303-10.
  3. Butbul-Aviel Y, Koren A, Halevy R, et al. Procalcitonin as a diagnostic aid in osteomyelitis and septic arthritis. Pediatr Emerg Care 2005;21(12):828-32.
  4. Fottner A, Birkenmaier C, von Schulze Pellengahr C, et al. Can serum procalcitonin help to differentiate between septic and nonseptic arthritis? Arthroscopy 2008;24(2):229-33.
  5. Hügle T, Schuetz P, Mueller B, et al. Serum procalcitonin for discrimination between septic and non-septic arthritis. Clin Exp Rheumatol 2008;26(3):453-456.