NEW YORK (Reuters Health) – In patients with autoimmune disease who develop fever, the serum procalcitonin (PCT) level has greater diagnostic value than the serum C-reactive protein (CRP) level in differentiating bacterial infection from disease flare, according a systematic review and meta-analysis of relevant research.
“Analysis of the pooled data suggests that PCT is a more specific indicator of bacterial infection than CRP, but that CRP is a more sensitive indicator of bacterial infection than PCT,” conclude Dr. Shy-Shin Chang, from Chang Gung University and Memorial Hospital in Taoyuan, Taiwan and colleagues in a report online now in Arthritis & Rheumatism.
Dr. Chang added in comments to Reuters Health, “The results showed a positive PCT result can confirm the infection, but a negative result does not exclude the possibility of infection. C-reactive protein, as expected, is not specific enough to confirm the infection.”
“It has to be noted,” Dr. Chang said, “that all of the studies used an old generation kit which cannot detect low serum level of PCT. This may partly explain the low sensitivity of PCT showed in our study. Whether the newer generation kit can raise the sensitivity needs to be confirmed in future studies.”
Distinguishing infection from disease flare in febrile patients with autoimmune diseases is “critically important but can be challenging,” the authors note in their paper. Giving additional or higher dosages of immunosuppressive drugs can ameliorate disease flare but can exacerbate infection, they explain.
Complicating matters, the clinical manifestations of disease flare and infection overlap and are identified by similar laboratory markers. The authors say there is “an urgent need for a reliable biomarker that provides high sensitivity and specificity for the early discrimination of infection from disease flare in febrile patients with autoimmune diseases.”
The study team systematically reviewed the evidence for the accuracy of the PCT test for this purpose. In healthy individuals, serum PCT is normally undetectable (<0.05 ng/mL), but the level increases rapidly after bacterial infection. In contrast to CRP, PCT does not rise with non-infectious inflammation or non-bacterial infections, making it a potentially useful marker to distinguish bacterial infection from disease flare in the setting of autoimmune disease.
Dr. Chang and colleagues included in their meta-analysis nine studies of PCT and five studies of CRP for identifying bacterial infection as a cause of fever in patients with various autoimmune diseases. The studies had data on 975 patients whose PCT was measured and 330 patients whose CRP was measured.
The data suggested that PCT has “better discrimination than CRP in the differentiation of bacterial infection” in the setting of autoimmune disease, the researchers report. In particular, the area under the receiver operating curve was higher for PCT (0.91; 95% CI: 0.88 – 0.93) than for CRP (0.81; 95% CI: 0.78 – 0.84).
In general, say the investigators, PCT is a highly specific test for identifying bacterial infection, more so than CRP, but it’s not as sensitive as CRP.
Pooled sensitivity was 0.75 (95% CI: 0.63 – 0.84) for PCT and 0.77 (95% CI: 0.67 – 0.85) for CRP.
Pooled specificity was 0.90 (95% CI: 0.85 – 0.93) for PCT and 0.56 (95% CI: 0.25 – 0.83) for CRP.
PCT had a high positive likelihood ratio (7.28; 95% CI 5.10 – 10.38), “making it sufficient to serve as a rule-in biomarker,” the investigators report, whereas CRP had a low positive likelihood ratio (1.76; 95% CI: 0.88 – 3.49), making it “unsuitable” as a rule-in test.
Both markers had suboptimal negative likelihood ratios and so are not suitable tests for excluding bacterial infection in febrile patients with autoimmune diseases, the study team says.
They note in their paper that different cut off levels are needed to optimize the discriminative capability of PCT for different autoimmune diseases. However, this requires a large study or studies of patients with the same autoimmune disease.
Until the results of such studies are available, they recommend using a standard PCT cut off value of 0.5 ng/mL, “which has reasonable sensitivity (76%) and specificity (88%).”
The study was supported by the National Science Council. The authors have no conflicts of interest.
Arthritis Rheum 2012.