Abstract

Introduction: Fecal calprotectin (FCP) is an inflammatory marker frequently used to monitor inflammatory bowel disease (IBD) activity, but it can also be elevated in gastrointestinal infections. The impact of infections on FCP level in people with IBD has not been well described across pathogens. The objective of our study was to quantify the relationship between FCP levels and lab-confirmed infections in people with and without IBD. Methods: We performed a retrospective cohort study at a tertiary-care referral center of inpatient and outpatient encounters during which FCR and gastrointestinal pathogen polymerase-chain reaction (GI PCR) testing were conducted. Using non-parametric tests and quantile regression, we compared FCP levels between individuals with and without IBD and with and without pathogen detection. Results: There were 3,399 encounters with FCP and GI PCR testing from 2,780 unique individuals between August 1, 2016 and February 17, 2022. Overall, 1819 (53.5%) encounters were individuals with IBD (n=1,819, Table). Pathogens were detected in 757 encounters (22.3%). There was no significant difference in pathogen detection or pathogen type between groups with and without IBD (p >0.9). The median FCP was 46 mg/kg in individuals without IBD and 265 mg/kg in those with IBD (p< 0.001). Among individuals without IBD, the median FCP was significantly elevated when a pathogen was detected (64 vs. 41 mg/kg, p=0.0003, Figure), but FCP was not significantly elevated among those with IBD when a pathogen was detected (299 vs. 255 mg/kg, p=0.207). After adjusting for age and IBD status in quantile regression, pathogen detection was only significantly associated with higher FCP in the lower two quartiles, though IBD remained significantly associated with higher FCP at all levels (p >0.001). After adjusting for IBD and age, FCP was significantly associated with detection of bacterial pathogens and multiple pathogens in the lower two quartiles. Conclusion: Pathogen detection by GI PCR is associated with elevated FCP, though this relationship is nonlinear and varies by IBD status. Even after stratifying by IBD status, there is significant variability in FCP, suggesting that factors in addition to infection may be playing a role, including potentially measurement error, or a greater immune reaction to pathogen infection in IBD leading to mild flares. Our findings indicate that FCP may be an adjunct to, but not a substitute for stool pathogen testing.Figure 1.: Fecal calprotectin levels by stool pathogen testing result and inflammatory bowel disease (IBD) diagnosis Table 1. - Characteristics of patients with and without IBD who had fecal calprotectin and gastrointestinal pathogen testing Variable OverallN = 3,347 1 IBD diagnosis p-value 2 No IBDN = 1,528 1 IBDN = 1,819 1 Fecal calprotectin (mg/kg) 107 (31, 498) 46 (24, 168) 265 (56, 903) < 0.001 Pathogen detected 744 (22%) 340 (22%) 404 (22%) >0.99 Age (years) 39 (25, 57) 41 (23, 61) 38 (26, 55) 0.02 Sex < 0.001 Female 2,013 (60%) 988 (65%) 1,025 (56%) Male 1,333 (40%) 540 (35%) 793 (44%) Race 0.13 African American 332 (9.9%) 135 (8.8%) 197 (11%) American Indian or Alaska Native 5 (0.1%) 3 (0.2%) 2 (0.1%) Asian 92 (2.8%) 51 (3.3%) 41 (2.3%) Caucasian 2,768 (83%) 1,277 (84%) 1,491 (82%) Native Hawaiian and Other Pacific Islander 1 (< 0.1%) 1 (< 0.1%) 0 (0%) Other 113 (3.4%) 49 (3.2%) 64 (3.5%) Patient Refused 18 (0.5%) 5 (0.3%) 13 (0.7%) Unknown 16 (0.5%) 7 (0.5%) 9 (0.5%) Ethnicity 0.35 Hispanic or Latino 89 (2.7%) 49 (3.2%) 40 (2.2%) Non-Hispanic or Latino 3,193 (96%) 1,449 (95%) 1,744 (96%) Patient Refused 22 (0.7%) 10 (0.7%) 12 (0.7%) Unknown 39 (1.2%) 18 (1.2%) 21 (1.2%) Inpatient encounter 1,435 (43%) 523 (34%) 912 (50%) < 0.001 1 Median (IQR); n (%) ; 2 Wilcoxon rank sum test; Pearson's Chi-squared test; Fisher's exact test.

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