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The Combination of Fecal Calprotectin with ESR, CRP and Albumin Discriminates More Accurately Children with Crohn's Disease

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The Combination of Fecal Calprotectin with ESR, CRP and Albumin Discriminates More Accurately Children with Crohn's Disease Advances in Medical Sciences 64 (2019) 9–14 Contents lists available at ScienceDirect Advances in Medical Sciences journal homepage: www.elsevier.com/locate/advms Original research article The combination of fecal calprotectin with ESR, CRP and albumin T discriminates more accurately children with Crohn’s disease ⁎ Urszula Daniluka, , Jaroslaw Danilukb, Milena Krasnodebskaa, Joanna Maria Lotowskac, Maria Elzbieta Sobaniec-Lotowskac, Dariusz Marek Lebensztejna a Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, Bialystok, Poland b Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland c Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland ARTICLE INFO ABSTRACT Keywords: Purpose: Increased fecal calprotectin is a sensitive marker of various types of intestinal inflammation. We in- Calprotectin vestigated correlations between high fecal calprotectin concentration and serum inflammatory markers in Intestinal infection children with different intestinal diseases with diarrhea with/without blood and/or abdominal pain, totest Food protein induced proctocolitis whether the combination of these markers can differentiate potential patients with inflammatory bowel disease. Crohn’s disease Materials/methods: The study included 128 children with high fecal calprotectin concentration (> 150ug/g) and Ulcerative colitis symptoms suggesting bowel disorders, hospitalized in the years 2013– 2015. Twenty-six (20%) patients were diagnosed with Crohn’s disease, 55 (43%) with ulcerative colitis, 32 (25%) with intestinal infection and 15 (12%) with food protein induced proctocolitis. Results: Significantly increased inflammatory markers were detected in children with inflammatory boweldis- ease, with a correlation between calprotectin and erythrocyte sedimentation rate – ESR (R = 0.53), mean cor- puscular volume – MCV (R=-0.64), red blood cell distribution width (R = 0.56), albumin (R = −0.52), he- moglobin (R = −0.53) only in Crohn’s disease patients. To discriminate Crohn’s disease patients from patients with intestinal infection and patients with food protein induced proctocolitis, AUC analysis was performed. It revealed that considering ESR, CRP and albumin as additional markers to fecal calprotectin significantly im- proved diagnostic performance (AUC 0.917, p = 0.038). Conclusions: In children with abdominal pain and/or diarrhea, increased ESR, CRP and decreased albumin combined with a high fecal calprotectin level yields additional diagnostic value in screening potential patients with Crohn’s disease. As far as differentiation of ulcerative colitis is concerned, low additional diagnostic value was found when high fecal calprotectin was combined with albumin. 1. Introduction reported in other diseases such as infectious diarrhea, necrotizing en- terocolitis, cow’s milk protein allergy, colorectal cancer, colonic polyps, In pediatric population, symptoms of inflammatory bowel disease a non-steroidal anti-inflammatory drug induced enteropathy, cystic fi- (IBD) do not differentiate this disease from other intestinal disorders. brosis, juvenile idiopathic arthritis, and even untreated celiac disease The gold standard in diagnosing IBD is colonoscopy [1]. However, this [2,7–9]. However, combining FC with serum markers of inflammation procedure is expensive and invasive. On the other hand, serum markers might prove valuable in distinguishing patients with IBD from in- of inflammation are insufficient for discriminating between IBDand dividuals with other intestinal disorders in whom high FC was detected. other intestinal inflammatory diseases [1]. It has been demonstrated It has already been shown that an increased FC level is a good predictor that a high level of fecal calprotectin (FC) is very sensitive (97%) but of intestinal inflammation, particularly when combined with an ele- moderately specific (71%) in diagnosing inflammatory bowel diseases vated C-reactive protein serum concentration, observed in adults and (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC) [2–6]. not-naïve IBD patients [10,11]. There are no published data concerning Moreover, according to literature reports, a high FC level has also been the association of FC with other commonly tested blood inflammatory ⁎ Corresponding author at: Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, J. Waszyngtona 17, 15-274 Bialystok, Poland. E-mail addresses: [email protected], [email protected] (U. Daniluk). https://doi.org/10.1016/j.advms.2018.08.001 Received 6 November 2017; Accepted 3 August 2018 Available online 18 September 2018 1896-1126/ © 2018 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved. U. Daniluk, et al. Advances in Medical Sciences 64 (2019) 9–14 markers, whose values are abnormal in IBD but not typically in other 2.2. Measurement of serum inflammatory markers intestinal diseases. The combination of these markers and FC might increase the predictive value of the test to screen patients with IBD Serum CRP (mg/L) and albumin (g/dL) levels were determined by before requesting endoscopic procedures. immunoturbidimetry (Abbott Diagnostics, Japan). The ESR was eval- Therefore, the aim of the study was to determine the correlation uated according to the Westergren method (mm/h). The complete between high FC concentration and serum inflammatory markers (C- blood count was measured using a Hematology Analyzer (Beckman reactive protein - CRP, erythrocyte sedimentation rate – ESR, white Coulter). The cut-off values of the biomarkers (ESR > 10 mm/h, blood count - WBC, platelet count - PLT, red blood cell distribution CRP > 5 mg/L, WBC > 10 × 103/uL, PLT > 350 × 103/uL, width - RDW, mean platelet volume – MPV, albumin) and complete Hb < 11 g/dL, MCV < 75 fL, RDW > 15%, MPV < 7 fL, blood count (hemoglobin – Hb, mean corpuscular volume – MCV) in Albumin < 3.5 g/dL) were based on the laboratory reference ranges of children with different intestinal diseases manifested with diarrhea the Medical University of Bialystok Children's Hospital (Poland). with or without blood and/or abdominal pain, in order to examine whether the combination of these markers can differentiate potential patients with IBD. 2.3. Measurement of fecal calprotectin 2. Materials and methods A parent of each child and the older children were provided with a plastic container and were instructed on how to collect stool samples. 2.1. Patient selection All fecal samples were collected during hospitalization, frozen and stored at - 80 °C immediately following receipt until analysis. FC con- The retrospective investigation included 138 children treated in the centration was determined by ELISA kit (IDK Calprotectin, Department of Pediatrics, Gastroenterology and Allergology and the Immundiagnostik, Bensheim, Germany) according to the manu- Gastroenterology Outpatient Clinic in the years 2013–2015 due to facturer’s instructions. The upper normal limit is determined as 50 μg of gastrointestinal (GI) tract symptoms such as abdominal pain, diarrhea calprotectin per 1 g of feces. with or without blood in the stool combined with high FC concentration (> 150 μg/g). This level of FC (exceeding the upper reference limit threefold) had previously been reported as a good predictor of IBD 2.4. Statistical analysis offering the highest sensitivity [12,13]. Despite elevated FC levels, 10 children were not included in the study since they were diagnosed with Data analysis was performed using the Statistica software. The re- juvenile polyps or the etiology of symptoms was unknown. sults are presented as median (min-max). Markers with a skewed dis- Based on the final diagnosis the participants were categorized into4 tribution (calprotectin, ESR, CRP and RDW) were log transformed. The groups: significance of difference in the data was evaluated with theMann- Whitney non-parametric U test Based on Spearman analysis, correla- 1 26 children with newly diagnosed CD, aged 5–17 years (17 male / 9 tions between the FC concentration and the selected parameters of female). Diagnosis was based on ESPGHAN guidelines, including complete blood count (Hb, MCV) and inflammatory markers (ESR, CRP, radiological, endoscopic and histological criteria [1]. Disease loca- albumin, PLT, RDW, MPV) were tested. tion, according to the Paris classification, was described as L1 (distal The diagnostic value of the markers combined with FC concentra- 1/3 ileum) in 12 patients (46%), L3- (ileocolonic) in 6 (23%), L4 tion was estimated using multivariate regression and ROC curves ana- (upper GI tract) in 1 (4%), L1 + L4 in 4 (15%) and L3 + L4 in 3 lyses. Some variables deviated significantly from normal distribution (12%) [14]. Disease activity, according to the pediatric CD activity (Shapiro-Wilk test) and therefore they were log-transformed to decrease index (PCDAI) [15], was scored as: severe (> 50pts) in 1 patient skewness. Log-transformed variables were: FC, ESR, CRP, MCV, al- (4%), moderate (30–50 pt s) in 8 (31%) and mild (< 30pts) in 17 bumin and RDW. To determine the combined diagnostic usefulness of children (65%). None of the patients was being treated at the time of sets of clinical covariates, synthetic indicators were developed. These diagnosis and collection of samples for tests. indicators are linear combinations of selected variables. Coefficients of 2 55 children with newly diagnosed UC, aged 1–17 years (27 male / these combinations
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