SLR - June 2018 - Emily Curley

The Role of Serum Procalcitonin, Interleukin-6 and Fibrinogen Levels in Differential Diagnosis of Diabetic Foot Ulcer Infection

Reference: Korkmaz P, Koçak H, Onbaşı K, et al. The Role of Serum Procalcitonin, Interleukin-6 and Fibrinogen Levels in Differential Diagnosis of Diabetic Foot Ulcer Infection. Journal of Diabetes Research. 2018;2018:7104352. doi:10.1155/2018/7104352.

Scientific Literature Review

Reviewed By: Emily Curley, DPM

Residency Program: Metrowest Medical Center, Framingham, MA

Podiatric Relevance: Incidence of diabetic foot ulcerations and associated infections is rising. Early detection of these infections is key for proper treatment and prevention of amputations. Wound guidelines, such as the Infectious Disease Society of America (IDSA) guidelines, along with well-known chemical biomarkers, such as Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP), aid in the diagnosis of an infected diabetic foot ulcer (IDFU). The authors evaluated the use of additional biomarkers, such as procalcitonin (PCT), fibrinogen and interleukin-6 (IL-6), in the differentiation of an infected diabetic foot ulceration (IDFU) versus a noninfected diabetic foot ulceration (NIDFU).

Methods: A study was performed in several specialty clinics in a single hospital system from January 1, 2016 to January 1, 2017. Inclusion criteria consisted of patients more than 18 years of age with a diagnosis of Type 2 Diabetes Mellitus who followed up in one of the clinics over the aforementioned time period. IDSA guidelines were utilized to separate patients into the following three groups: IDFU, NIDFU and diabetic without an ulcer (control group). Exclusion criteria consisted of patients with other systemic or localized infections, systemic inflammatory disease or patients on immunosuppressive treatment. The presence of purulent discharge or the presence of two or more inflammatory clinical findings were used as evidence for infection. IDSA guidelines were utilized to determine infection. Demographic information for all patients was obtained. All patients underwent fasting blood samples, which included a complete blood count (CBC), ESR, Hemoglobin A1c, fasting blood glucose, CRP, PCT, IL-6 and fibrinogen levels. All blood samples were handled following specific protocol in a blinded fashion. Imaging, probe-to-bone test, deep tissue culture and advanced imaging were performed as deemed necessary by the physicians. Various statistical tests were utilized to measure significance, which was set at a level of p<0.05.

Results: 119 total patients were included in this study; 38 patients with an IDFU, 38 patients with a NIDFU and 43 controls. The mean age was 61.07 + 11.04 years. Fifty-six percent were males. All of the following blood tests were found to be significantly higher in IDFUs versus NIDFUs and the control: WBC, ESR, CRP, IL-6 and fibrinogen. All of the aforementioned blood levels were also found to be significantly higher in NIDFU versus control group. There was, however, no significant difference in measurement of PCT between the three groups.

Conclusions: The authors concluded that IL-6 and fibrinogen may be useful inflammatory biomarkers in the determination of an IDFU versus NIDFU along with the established markers of ESR and CRP. They found that PCT may be less helpful in the determination of an IDFU. IL-6 is a cytokine that works in the induction of CRP and fibrinogen synthesis in the liver during bacterial infection. It is an inexpensive test and may be useful in the determination of an IDFU. In the case of a DFU, thorough clinical evaluation is essential for early detection and appropriate management. The use of inflammatory markers should be used on a case-by-case basis. Further studies for these biomarkers in the differentiation between mild, moderate and severe IDFUs could shed a new light on treatment protocol. 

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