The incidence of acute pancreatitis (AP) in children has been increasing over time, and better modeling is needed to predict severe AP in this population. In this study, children with AP were recruited prospectively at a tertiary children’s hospital in the United States. AP was defined as occurring when a child had two of the following three criteria: abdominal pain consistent with AP, serum amylase or lipase level greater than 3 times the upper limit of normal, and imaging consistent with AP. A “derivation cohort” consisted of patients presenting with AP between 2016 and 2018 while a “validation cohort” consisted of patients diagnosed with AP between 2018 and 2019. Blood sampling was obtained within 48 hours of hospital admission for AP which then underwent analysis for the presence of multiple protein biomarkers (via the Luminex® assay), and C-reactive protein (CRP) levels were measured as well. Severity of pediatric pancreatitis was determined by pre-existing North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) guidelines.
The derivation cohort consisted of 46 patients with AP and 20 control patients while the validation cohort consisted of 25 patients with AP and 10 control patients. No significant difference in age, sex, body mass index, etiology of AP, or AP severity was present between groups. Heatmap analysis demonstrated 48 biomarkers that were statistically significant when comparing patients with AP with controls. Specifically, Interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) levels were significantly higher in patients with severe AP in the derivation cohort compared to patients with mild AP and with controls. This testing was repeated in the validation cohort, and again, IL-6 and MCP-1 levels were significantly elevated in patients with severe AP compared to patients with mild AP as well as with controls. CRP levels were significantly higher in both the derivation cohort and validation cohort for patients with severe AP compared to patients with mild AP and controls. The absolute neutrophil count, absolute lymphocyte count, and absolute monocyte count were significantly higher in the validation cohort for patients with severe AP compared to patients with mild AP and to control patients. Interestingly, ROC modeling demonstrated that blood urea nitrogen (BUN) levels were statistically correlated with severity of AP with a good area under the receiver operating characteristic (AUROC 0.72 [95% CI 0.57-0.87], P = .003), and BUN combined with CRP improved the model to a greater degree (AUROC 0.79 [95% CI 0.64-0.94]). Similar significant findings were noted when BUN was combined independently with IL-6 and MCP-1.
This study suggests that CRP levels are helpful in predicting severity in pediatric patients with acute recurrent pancreatitis which can then help guide therapy. IL-6 and MCP-1 are novel proteins that may prove to be useful as additional biomarkers for future studies.
Farrell P, Jones E, Hornung L, Thompson T, Patel J, Lin T, Nathan J, Vitale D, Habtezion A, Abu-El-Haija M. Cytokine profile elevations on admission can determine risks of severe acute pancreatitis in children. Journal of Pediatrics 2021; 238: 33-41.