This study demonstrates that elevated levels of CRP are found in a significant portion of patients hospitalized with IMN without bacterial co-infection.
The mechanisms underlying the induction of CRP synthesis in different circumstances are still to be explored. Cytokines such as interleukin-6 and tumor necrosis factor-alpha have been shown to be involved [6–10], but their relation to specific characteristics of the offending microorganism is unknown. Exceptionally high levels have been reported in patients with adenovirus [2, 11] and herpes simplex virus (HSV) infections [12].
Since adenovirus and HSV are hepatotrophic viruses, and CRP is synthesized in the liver, our hypothesis was that the distribution of CRP levels would be similarly elevated in patients infected by other hepatotrophic viruses - EBV and CMV. The results presented in the current study support the hypothesis of a general relation between hepatotrophic viral infections and elevated CRP levels, relative to historic cohorts of patients with respiratory virus infections [13], and similar to bacterial infections.
Although CRP may support clinical decisions when the differential diagnosis includes viral and bacterial infections, the extent of its application is controversial[13–16] due to the relatively high gap between specificity and sensitivity, independent of the threshold used. This gap is the result of overlap between CRP values distribution related to different conditions.
Our results may aid clinicians by suggesting that elevated CRP levels in a clinical context implying infection caused by hepatotrophic viruses (e.g. conjunctivitis for adenovirus, oral aphtha for HSV, rash, lymphadenopthay and/or elevated liver enzymes for IMN) do not necessarily indicate bacterial co-infection, and antibiotic therapy may be withheld.
However, CRP remains important in patients lacking clinical signs and laboratory results implying a possible hepatotrophic viral infection. In the relevant clinical scenarios, such as fever without localizing signs or patients with pneumonia, CRP levels of 5 mg/dL and above support the possibility of bacterial infection and decisions to initiate empirical antibiotic therapy [2, 4, 13, 14].
To the best of our knowledge, this work is the first to systematically evaluate CRP values in patient with IMN. The retrospective nature of this work and the characteristics of its population preclude definitive conclusions regarding the distribution of CRP among IMN patients in the community. However, even if the results refer to a subpopulation of IMN patients, the general conclusions and recommendations presented above remain relevant.