The purpose of this study was to examine the utility of small bowel capsule endoscopy (SBCE) in the diagnostic pathway of patients that had elevated fecal calprotectin (FC) and normal colonoscopy.

Patients with elevated FC and normal colonoscopy that underwent SBCE in the last 4 years were included. Patients were divided into 3 groups: group 1: patients with isolated small bowel Crohn's disease (SBCD) on SBCE; group 2: patients with elevated FC but normal SBCE; and group 3: patients with isolated terminal ileitis.

The study included 320 patients (group 1: 254 patients, group 2: 50 patients, and group 3: 16 patients). The median age was 42.5 years (IQR 26) across the three groups and 52.4% of the patients had a new diagnosis of SBCD. In group 1, active disease was identified distally in 247 patients (77.2%), proximal involvement in 90 patients (28.1%), and extensive SBCD in 68 patients (21.3%). Magnetic resonance enterography (MRE) was carried out in 229 (90.1%) patients in group 1 and was negative in 42 patients with SBCD. The diagnostic yield of SBCE was higher than that of MRE (p < 0.0001). In group 2, the final diagnoses included Helicobacter pylori infection (n = 2), NSAID use (n = 3), celiac disease (n = 2), and microscopic colitis (n = 1). The final diagnoses in group 3 were idiopathic terminal ileitis (n = 11), inflammatory bowel disease (n = 3), and infective terminal ileitis (n = 2).

SBCE influences the patient pathway even when negative/normal. It is better at identifying early SBCD, when compared with MRE.

Fecal calprotectin (FC) is a non-invasive biomarker of gut inflammation, but its role in celiac disease (CD) and non-celiac enteropathies (NCEs) is undefined.

To retrospectively evaluate FC in patients with CD and NCEs as a tool for assessing disease activity and predicting long-term outcomes.

Patients with uncomplicated and complicated CD, and NCEs with data on FC, evaluated at our center between June-2008 and December-2023, were enrolled. The relationship between elevated FC (>50 mg/kg) and disease activity was statistically analysed and Cox regression adjusted for age and sex was used to compare development of complications and mortality in patients with elevated and normal FC.

177 patients (109F, mean age at diagnosis 39±20 years, 132 CD, 17 complicated CD, 28 NCEs) were enrolled. 55 patients had elevated FC, which was associated with lack of clinical and histological response to therapy (both p < 0.001). During a median follow-up of 103 months (IQR 54-176), 22 patients developed complications (15.4 %) and 21 died (11.9 %). Elevated FC was significantly more common in complicated CD (70.6 %) and NCEs (67.9 %) than in uncomplicated CD (18.2 %), p < 0.001. Elevated FC was independently predictive of developing complications (HR 4.8,95 %CI 1.4-17.7, p = 0.01) and mortality (HR 4.8,95 %CI 1.6-14.3, p < 0.01).

FC is a promising non-invasive biomarker for assessing disease severity and long-term outcomes in CD and NCEs.

In coeliac disease and environmental enteropathy, dietary gluten and enteric infections cause reversible inflammation and morphological changes to the small intestinal mucosa that can be detected in biopsy samples obtained by endoscopy. However, there is a clear need for non-invasive biomarkers. Constant shedding of mucosal material into the bowel lumen and faeces, together with easy availability of stool, makes it an interesting sample matrix.

To conduct a systematic literature search and summarize the existing evidence for host mucosa-derived faecal biomarkers in evaluating small intestinal damage.

We searched for studies on PubMed (MEDLINE) until 1 March 2024.

We identified 494 studies and included 35 original case-control and cohort studies. These assessed host mucosal transcripts and 14 other markers aiming specifically to reflect inflammation and cell-mediated, innate and gluten-induced immune responses. In coeliac disease, faecal calprotectin and anti-gliadin, tissue transglutaminase, endomysium and deamidated gliadin peptide antibodies were the most studied but with inconsistent results. Single studies reported positive findings about microRNA transcripts, β-defensin-2, lipocalin-2, zonulin-related proteins and angiotensin-converting enzyme. In environmental enteropathy, a non-significant association was reported between calprotectin and urine lactulose/mannitol ratio; there were conflicting results for neopterin, myeloperoxidase and host transcripts. Single studies reported a positive association for lactoferrin, and a negative association for regenerating islet-derived protein 1. Studies comparing faecal markers against small intestinal biopsy findings were not identified in environmental enteropathy.

Further studies are needed to determine reliable faecal markers as a proxy for small intestinal mucosal damage.

Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases. However, its role, pros, and cons in various conditions must be comprehensively elucidated.

To explore the role of fecal calprotectin in pediatric gastrointestinal diseases, including its advantages and limitations.

A comprehensive search was conducted on PubMed, PubMed Central, Google Scholar, and other scientific research engines until February 24, 2024. The review included 88 research articles, 56 review articles, six meta-analyses, two systematic reviews, two consensus papers, and two letters to the editors.

Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders, inflammatory bowel disease, coeliac disease, coronavirus disease 2019-induced gastrointestinal disorders, gastroenteritis, and cystic fibrosis-associated intestinal pathology. However, its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation. Despite these limitations, fecal calprotectin offers significant advantages in diagnosing, monitoring, and managing pediatric gastrointestinal diseases.

Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology, offering insights into disease activity, treatment response, and prognosis. Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges. Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.

Celiac disease, an autoimmune disorder induced by the ingestion of gluten, affects approximately 1.4% of the population. Gluten damages the villi of the small intestine, producing symptoms such as abdominal pain, bloating and a subsequent loss of nutrient absorption, causing destabilization of the nutritional status. Moreover, gluten can trigger extra intestinal symptoms, such as asthma or dermatitis, but also mental disorders such as depression or anxiety. Moreover, people suffering from celiac disease sometimes feel misunderstood by society, mainly due to the lack of knowledge about the disease and the gluten-free diet. Thus, the treatment and follow-up of patients with celiac disease should be approached from different perspectives, such as the following: (1) a clinical perspective: symptomatology and dietary adherence monitorization; (2) nutritional assessment: dietary balance achievement; (3) psychological assistance: mental disorders avoidance; and (4) social inclusion: educating society about celiac disease in order to avoid isolation of those with celiac disease. The aim of this narrative review is to gain deep insight into the different strategies that currently exist in order to work on each of these perspectives and to clarify how the complete approach of celiac disease follow-up should be undertaken so that the optimum quality of life of this collective is reached.

Celiac disease (CeD) is an autoimmune condition triggered by gluten in genetically predisposed individuals, affecting all ages. Intestinal permeability (IP) is crucial in the pathogenesis of CeD and it is primarily governed by tight junctions (TJs) that uphold the intestinal barrier's integrity. The protein zonulin plays a critical role in modulating the permeability of TJs having emerged as a potential non-invasive biomarker to study IP. The importance of this study lies in providing evidence for the usefulness of a non-invasive tool in the study of IP both at baseline and in the follow-up of paediatric patients with CeD. In this single-centre prospective observational study, we explored the correlation between faecal zonulin levels and others faecal and serum biomarkers for monitoring IP in CeD within the paediatric population. We also aimed to establish reference values for faecal zonulin in the paediatric population. We found that faecal zonulin and calprotectin values are higher at the onset of CeD compared with the control population. Specifically, the zonulin levels were 347.5 ng/mL as opposed to 177.7 ng/mL in the control population (p = 0.001), while calprotectin levels were 29.8 μg/g stool compared to 13.9 μg/g stool (p = 0.029). As the duration without gluten consumption increased, a significant reduction in faecal zonulin levels was observed in patients with CeD (348.5 ng/mL vs. 157.1 ng/mL; p = 0.002), along with a decrease in the prevalence of patients with vitamin D insufficiency (88.9% vs. 77.8%). We conclude that faecal zonulin concentrations were higher in the patients with active CeD compared with healthy individuals or those following a gluten-free diet (GFD). The significant decrease in their values over the duration of the GFD suggests the potential use of zonulin as an additional tool in monitoring adherence to a GFD.

Celiac disease is an autoimmune disorder in which the immune system of genetically susceptible individuals elicits a reaction to gluten causing small intestine damage. If left undiagnosed and untreated, the resulting nutrition malabsorption can lead to anemia, bone disease, growth faltering, or other consequences. The condition is lifelong and lacks a cure; the only treatment is lifelong adherence to a gluten-free diet (GFD). This diet is challenging to follow and adversely influences quality of life; however, it is essential to ensure intestinal recovery and prevent future negative health consequences. The Academy of Nutrition and Dietetics convened an expert panel complemented by a celiac disease patient advocate to evaluate evidence for six topics, including medical nutrition therapy; the GFD; oat consumption; micronutrients; pro-/prebiotics; and the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet. This publication outlines the Academy of Nutrition and Dietetics Evidence Analysis Library methods used to complete the systematic review and guideline development, and summarizes the recommendations and supporting evidence. The guidelines affirm that all individuals with celiac disease should follow a GFD (1C, Imperative) that may include gluten-free oats in adults (2D, Conditional). Children should follow a nutritionally adequate GFD that supports healthy growth and development (Consensus, Imperative) and does not unnecessarily restrict gluten-free oats (Consensus, Conditional). The guidelines indicate nutritional care should include routine nutritional assessment (Consensus, Imperative) and medical nutrition therapy (Consensus, Imperative). At this time, the guidelines do not support a recommendation for the addition of the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (2C, Conditional); prebiotic or probiotic supplementation (2D, Conditional); or micronutrient supplementation (in the absence of nutritional deficiency) (Consensus, Conditional). The 2021 Celiac Disease Evidence-Based Nutrition Guideline will assist registered dietitian nutritionists in providing appropriate evidence-based medical nutrition therapy to support people with celiac disease in achieving and maintaining nutritional health and avoiding adverse celiac disease consequences throughout their lives.

Celiac disease (CD) is an intestinal disease that develops in genetically predisposed individuals and is triggered by the ingestion of gluten. CD was considered a Th1-disease. Today, the role of Th17, IL-21, and IL-17A lymphocytes is well known. Inflammation is regulated by the activity of gluten-specific CD4+ T lymphocytes that produce pro-inflammatory cytokines, including IFN-γ, TNF-α, and IL-21, perpetuating the Th1 response. These cytokines determine an inflammatory state of the small intestine, with consequent epithelial infiltration of lymphocytes and an alteration of the architecture of the duodenal mucosa. B cells produce antibodies against tissue transglutaminase and against deamidated gliadin. Although the role of the adaptive immune response is currently known, the evidence about the role of innate immunity cells is still poorly understood. Epithelial damage determines the release of damage-associated molecular patterns (DAMPs), also known as alarmins. Together with the intestinal epithelial cells and the type 1 innate lymphoid cells (ILC1s), alarmins like TSLP, IL-33, and HMGB1 could have a fundamental role in the genesis and maintenance of inflammation. Our study aims to evaluate the evidence in the literature about the role of ILCs and alarmins in celiac disease, evaluating the possible future diagnostic and therapeutic implications.

Circulating tissue transglutaminase IgA (TTG IgA) concentrations are sensitive and specific indicators of celiac disease, but discrepancies between serologic and histologic findings still occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as non-invasive means of evaluating disease activity.

Participants with positive celiac serologies and controls with negative celiac serologies were enrolled at the time of upper endoscopy. Blood, stool and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin and alpha-1-antitrypsin and plasma lipcalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and TTG IgA concentration.

Lipocalin-2 was significantly elevated in the stool ( p =0.007) but not the plasma of participants with positive celiac serologies compared to controls. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100mg/dL was specific, but not sensitive for biopsy proven celiac disease.

Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role in the local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease and did not correlate with degree of histologic changes on biopsy. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared to controls, an elevation of greater than 100mg/dL was 90% specific for biopsy proven celiac disease.

Celiac disease (CD) is an immune-mediated disorder of the gut in which innate and adaptive responses are involved. Antimicrobial peptides (AMPs) constitute an arsenal of innate immunity regulators of paramount importance in the gut. However, the role of AMPs in CD is unclear.

To evaluate the levels of fecal β-defensin-2, fecal calprotectin (FC), and antibodies against bactericidal/permeability-increasing protein (BPI) in the serum of children with active CD and to compare them with those of healthy controls (HCs).

We examined 76 children with recently diagnosed CD between the age of 2-10 years (average age: 6.1 ± 1.2 years) and 32 HC (average age: 6.2 ± 3.8 years) in this study. We evaluated the level of fecal β-defensin-2 and FC levels in coprofiltrates, and the level of anti-BPI antibodies in blood serum. Correlation relationships between the parameters were assessed according to Pearson correlation coefficient.

Fecal β-defensin-2 concentration was greater in the CD group than in HC group, amounting to 99.6 ± 15.5 ng/mL and 64.0 ± 2.4 ng/mL, respectively (p < 0.02). The level of FC in the CD children was 35.4 ± 8.1 μg/g, while that in the control group was 19.1 ± 1.1 μg/g, (p < 0.05), representing a slightly increase. The concentration of anti-BPI antibodies in the CD and HC groups was 35.9 ± 10.1 U/mL and 5.2 ± 3.2 U/mL, respectively (p < 0.002). There was a strong and direct correlation between fecal β-defensin-2 and FC (r = 0.69), as well as a direct but weak relationship between fecal β-defensin-2 and anti-BPI antibodies (r = 0.35).

Our data reinforce that fecal β-defensin-2 and anti-BPI antibodies are greatly increased in patients with active CD. These biomarkers may be components of epithelial innate immunity in the intestine, with each having a distinct functional role in intestinal6 mucosal defense.

Although endoscopy is the gold standard to assess disease activity and infliximab efficacy in inflammatory bowel disease (IBD), the invasive, costly, and time-consuming procedure limits its routine applications. We aimed to investigate the clinical value of serum oncostatin M (OSM) as a surrogate biomarker.

Fifty healthy controls, 34 non-IBD patients, and 189 IBD patients who were pre-infliximab treatment (n = 122) or in infliximab maintenance (n = 67) were enrolled. A chemiluminescence immunoassay (CLIA) was constructed to quantify serum OSM concentrations. Receiver operator characteristic (ROC) curve analysis was used to evaluate the performance of blood biomarkers for IBD management.

The methodology of CLIA exhibited great analytical performance with a wide linear range of 31.25-25000 pg/mL, a low detection limit of 23.2 pg/mL, acceptable precision, and applicable accuracy. Patients with IBD (121.5 [43.3-249.4] pg/mL, p < 0.001) and non-IBD (72.4 [51.4-129.6] pg/mL, p = 0.005) had higher serum OSM levels than healthy controls (35.8 [23.2-56.4] pg/mL). In the analysis of clinical and endoscopic activity, serum OSM levels were elevated in moderate and severe patients compared to those in remission. IBD patients without mucosal healing had higher serum OSM levels than those with mucosal healing (AUC = 0.843). Besides, serum OSM levels were increased in clinical non-responders (287.3 [127.9-438] pg/mL) compared to responders (24.1 [23.2-53.4] pg/mL, p < 0.001), and showed great recognition ability with an AUC of 0.898.

The newly developed methodology of CLIA had great potential for use in the clinic. Elevated serum OSM expression was a promising biomarker of severe disease and infliximab non-response in IBD patients.

Celiac disease (CD) is a chronic gluten-responsive immune mediated enteropathy and is treated with a gluten-free diet (GFD). However, a strict diet for life is not easy due to the ubiquitous nature of gluten. This review aims at examining available evidence on the degree of adherence to a GFD, the methods to assess it, and the barriers to its implementation. The methods for monitoring the adherence to a GFD are comprised of a dietary questionnaire, celiac serology, or clinical symptoms; however, none of these methods generate either a direct or an accurate measure of dietary adherence. A promising advancement is the development of tests that measure gluten immunogenic peptides in stools and urine. Causes of adherence/non-adherence to a GFD are numerous and multifactorial. Inadvertent dietary non-adherence is more frequent than intentional non-adherence. Cross-contamination of gluten-free products with gluten is a major cause of inadvertent non-adherence, while the limited availability, high costs, and poor quality of certified gluten-free products are responsible for intentionally breaking a GFD. Therefore, several studies in the last decade have indicated that many patients with CD who follow a GFD still have difficulty controlling their diet and, therefore, regularly consume enough gluten to trigger symptoms and damage the small intestine.

The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children.

A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors.

A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9.

Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schönlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.

Gastrointestinal tract symptoms such as abdominal pain, constipation, diarrhea, and fever are common reasons for which parents take children to the pediatrician. An increasing prevalence of chronic diseases of the gastrointestinal tract and a decrease in the median age of their onset indicate the need to search for new diagnostic methods for differentiating inflammatory bowel diseases (IBDs) from other gastrointestinal tract diseases. An example of a novel biomarker is fecal calprotectin (FC), which is considered a noninvasive and useful marker of intestinal inflammation. This review summarizes currently available information on the use of FC in the diagnosis and monitoring of IBD in children. Additionally, it attempts to determine the course of action depending on the concentration of FC. Application of FC determination within the framework of primary medical care can decrease the number of children unnecessarily referred either to endoscopic or radiologic examination. There is a double advantage of calprotectin screening; for patients, it reduces delays in diagnosis and unnecessary exposure to endoscopy, and for doctors, it reduces pressure on endoscopy testing and facilitates decision-making. We emphasize the role of FC as a noninvasive marker, primarily in patients with IBD, in monitoring disease activity, predicting relapse, monitoring therapy efficacy, and monitoring postoperative relapses.

It is still unknown whether faecal calprotectin elevation may be caused by active untreated coeliac disease (CD) itself or whether it indicates the coexistence of CD and another disease associated with gastrointestinal inflammation.

To assess faecal calprotectin concentration (FCC) and its correlation with the clinical form and histopathological picture of the small intestine in children with CD.

Fifty-five children with newly recognised CD (mean age: 9.1 years) and 17 children with CD diagnosed at least year before and on a strict gluten-free diet (mean age: 12.3 years) were accepted for the study. Classical (n = 27), non-classical (n = 17), and asymptomatic form (n = 11) were distinguished in children with newly diagnosed CD based on the clinical picture. The histopathological small intestinal lesions were classified as Marsh 1 (n = 4), 3a (n = 5), 3b (n = 20), and 3c (n = 26). FCC was assessed using ELISA method with 50 µg/g as the upper limit of the normal.

FCC was abnormal for 21 patients with newly diagnosed CD (38.2%) and for six patients from the treated group (35.3%). Mean FCC for the analysed group of patients was 91.7 ±144.8 µg/g, in the group with newly diagnosed CD - 100.9 ±154.4 µg/g, and in the treated group - 61.8 ±106.2 µg/g (Z = -1.333; p = 0.183). In the group of patients with recently diagnosed CD a statistically significant relationship was not observed for FCC and both clinical picture (χ² = 0.319, p = 0.852) and severity of small intestinal lesions according to the Marsh classification (rho = 0.136).

Assessment of FCC seems to have no use as a marker for diagnostics and monitoring of CD irrespective of clinical form of the disease and severity of the inflammatory lesions within the small intestine.

Fecal calprotectin (FC) is an inflammatory marker released mainly from gastrointestinal granulocytes measured in stool samples. FC is noninvasive, economical, simple, and acceptable for patients. Levels of FC have proven reliable for intestinal inflammation, with good clinical sensitivity, and are useful in screening and monitoring inflammatory bowel disease (IBD), as well as in the differential diagnosis between IBD and irritable bowel syndrome (IBS). Given its advantages, FC represents an attractive biomarker that could be utilized in various gastrointestinal (GI) diseases apart from IBD, and is currently being studied extensively by many research groups with significant amounts of data emerging. In this current review we aim to provide an outline of the utility of FC in distinguishing between IBS and IBD, as well as an up-to-date summary of the available clinical experience concerning FC in various common conditions of the GI tract commonly encountered by gastroenterology practitioners, such as IBS, microscopic colitis, acute gastroenteritis, Clostridium difficile infection, colorectal cancer, diverticular disease, coeliac disease, and other GI conditions.

Gluten-free diet (GFD) is the only management for coeliac disease (CD). Available methods to assess GFD compliance are insufficiently sensitive to detect occasional dietary transgressions that may cause gut mucosal damage. We aimed to develop a method to determine gluten intake and monitor GFD compliance in patients with CD and to evaluate its correlation with mucosal damage.

Urine samples of 76 healthy subjects and 58 patients with CD subjected to different gluten dietary conditions were collected. A lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant gluten immunogenic peptides (GIP) and a LFT reader were used to quantify GIP in solid-phase extracted urines.

GIP were detectable in concentrated urines from healthy individuals previously subjected to GFD as early as 4-6 h after single gluten intake, and remained detectable for 1-2 days. The urine assay revealed infringement of the GFD in about 50% of the patients. Analysis of duodenal biopsies revealed that most of patients with CD (89%) with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed incomplete intestinal mucosa recovery.

GIP are detected in urine after gluten consumption, enabling a new and non-invasive method to monitor GFD compliance and transgressions. The method was sensitive, specific and simple enough to be convenient for clinical monitoring of patients with CD as well as for basic and clinical research applications including drug development.

NCT02344758.

Calprotectin is a fecal marker of intraintestinal inflammation derived from activated enteric neutrophils and macrophages. It is useful as a clinical marker in inflammatory bowel diseases; furthermore, it may have a role in public health epidemiology.

The aim of the study was to describe the distribution of fecal calprotectin in Guatemalan preschool children sharing a common institutional diet; to relate it collectively to pediatric distributions in other geographic settings, and individually to concomitant indicators of intestinal infection or colonization and other descriptive features of the child.

Fecal samples were collected in 87 subjects, ages 2 to 7 years across 3 daycare centers sharing a common institutional menu, but from different ecological settings. Stools were examined, variously by routine light microscopy, quantitative egg counts, and a Giardia antigen test, for microbiological diagnosis, and an ELISA assay for fecal calprotectin (CalproLab).

The median fecal calprotectin value was 58 mg/kg, with a mean of 98 ± 136 mg/kg and a range from 10 to 950 mg/kg; 61% of values were above the manufacturer's cut-off for elevated concentration and 51% exceeded an age-adjusted criterion. There were no associations between sex, age, growth indicators, or fecal microbiological findings by microscopy or ELISA assays, alone or in combination. The central tendency (mean or median) and distribution were generally shifted to the right in relation to comparable reports from children across the world literature.

Although specific, low-grade intestinal infections do not define calprotectin subgroups, right-shifted fecal calprotectin status in this population may reflect a general and diffuse stress of adverse environmental sanitation.

Gluten-free diet (GFD) is the only treatment for celiac disease (CD). There is a general consensus that strict GFD adherence in CD patients leads to full clinical and histological remission accompanied by improvement in quality of life and reduced long-term complications. Despite the importance of monitoring the GFD, there are no clear guidelines for assessing the outcome or for exploring its adherence. Available methods are insufficiently accurate to identify occasional gluten exposure that may cause intestinal mucosal damage. Serological tests are highly sensitive and specific for diagnosis, but do not predict recovery and are not useful for follow-up. The use of serial endoscopies, it is invasive and impractical for frequent monitoring, and dietary interview can be subjective. Therefore, the detection of gluten immunogenic peptides (GIP) in feces and urine have been proposed as new non-invasive biomarkers to detect gluten intake and verify GFD compliance in CD patients. These simple immunoassays in human samples could overcome some key unresolved scientific and clinical problems in CD management. It is a significant advance that opens up new possibilities for the clinicians to evaluate the CD treatment, GFD compliance, and improvement in the quality of life of CD patients.

The present study aimed to provide evidence on whether children at risk of gastrointestinal inflammation have increased measurements of faecal calprotectin (FC). FC was measured in 232 children; 55 children (n = 11 treatment naïve) with juvenile idiopathic arthritis (JIA), 63 with coeliac disease (CD); 17 with new diagnosis before and after treatment on gluten-free diet and 114 controls. None of the treatment-naive children with JIA had raised FC. Four JIA patients on treatment had a raised FC but in all cases a repeat test was normal. In newly diagnosed patients with CD, the median (interquartile range) FC was higher 36.4 (26-61) than that in controls 25.0 (23-41) mg/kg (P = 0.045) but this significantly decreased 25 (25-25) mg/kg (P = 0.012) after 6 months on gluten-free diet. Random measurements of FC are not raised in children with JIA or CD. A significant elevation of FC in these groups is not explained by their diagnosis and therefore needs further investigation.

As seen over the past 20 years, calprotectin has evolved as a novel, non-invasive biomarker of gastrointestinal (GI) inflammation. We present this review of calprotectin in pediatrics. This article will focus on studies using calprotectin concentrations from different body fluids to monitor inflammation in different disease states and conditions. The ultimate goal of our group is to lay down a foundation as we consider using calprotectin prospectively as a marker of intestinal inflammation that could lead to further testing and possibly a marker of preparedness for feeding. We surveyed all published studies in English of calprotectin in neonates, infants, children, and adolescents through February 2014. We will discuss calprotectin's basic properties and analysis such as characteristics, identification, presence in body fluids, and maturational development. In addition, calprotectin's use in inflammatory diseases exploring both GI and non-GI conditions will be evaluated and compared with other serum markers presently available. Finally, a summary of our findings and discussion of future work that could be undertaken in order to render calprotectin as a more useful monitoring tool to the medical research community will complete the review.

Given the number of inflammatory disorders affecting the gastrointestinal tract directly and indirectly, coupled with the considerable overlap with functional disorders, it is evident that more useful noninvasive diagnostic tests are required to aid with diagnosis. If these tests can also have some utility for individual patient follow-up in terms of disease activity and response to treatment, as well as providing forewarning of disease relapse, it would be extremely useful information for the clinician. One recently described test that may fulfill several of these attributes is based on leakage of a mononuclear cell cytoplasmic protein, calprotectin, along the intestinal tract, which can then be quantified in feces. This has been used to distinguish patients exhibiting symptoms of irritable bowel syndrome from patients with inflammatory bowel disease, with a measure of success greater than with currently used techniques. The present article summarizes the experience with this test used in inflammatory bowel disease, as well as a variety of gastrointestinal disorders.

Among the adverse reactions caused by wheat, celiac disease (CD) is the longest studied and best-known pathology. The more recently defined non-celiac gluten sensitivity (NCGS) presents with symptoms which are often indistinguishable from CD. Diagnosis of CD is based on serologic, molecular, and bioptic testing. The IgA anti-transglutaminase (tTG) test is considered highly important, as it shows high sensitivity and specificity and its levels correlate to the degree of intestinal damage. Small bowel biopsy can be avoided in symptomatic patients with IgA anti-tTG levels above 10× the manufacturer's cut-off. Recently, tests of anti-deamidated peptides of gliadin (DGP) have replaced classic anti-native gliadin (AGA) tests. DGP assays have a considerably higher diagnostic accuracy than AGA assays, especially in the IgG class, and can replace anti-tTG tests in patients with selective IgA deficiency. The combination of IgG anti-DGP plus IgA anti-tTG assays show greater sensitivity than a single test, with very high specificity. EMA tests have great diagnostic accuracy but are not recommended by all the latest guidelines because they are observer dependent. Biopsy must still be considered the gold standard for CD diagnosis. HLA-DQ genotyping can be used to screen asymptomatic children and in cases of histology/serology disagreement. About half of NCGS patients are DQ2 positive and have IgG AGA. To diagnose NCGS, first CD and wheat allergy must be excluded; then the wheat dependence of symptoms must be verified by a gluten-free diet and subsequent gluten challenge.

Diagnosis and monitoring of inflammatory bowel diseases rely on clinical, endoscopic, and radiologic parameters. Inflammatory biomarkers have been investigated as a surrogate marker for endoscopic diagnosis of inflammatory activity. Fecal inflammatory biomarkers such as calprotectin and lactoferrin are direct products of bowel inflammation and provide an accurate and noninvasive diagnostic and monitoring modality for Crohn's disease and ulcerative colitis. This report contains an overview of the currently existing literature pertaining to clinical implications of fecal biomarkers for diagnosis, monitoring, and prediction of outcomes of inflammatory bowel disease.

Abdominal discomfort including pain, bloating and diarrhea is common. It often arises from functional gastrointestinal disorders but may indicate inflammatory bowel disease (IBD). Calprotectin is an abundant neutrophil protein that is released during inflammation. When measured in feces, it can be used to differentiate between non-organic and inflammatory intestinal disorders, especially to identify IBD. Fecal calprotectin might also be useful to monitor patients with IBD under treatment and to predict the risk of recurrence of active disease prior to clinical relapse. The use of fecal calprotectin has been investigated in a number of gastrointestinal disorders other than IBD, for example, as screening test for colorectal cancer but the available data are limited. This article summarizes the current literature on the use of fecal calprotectin in clinical practice.

Calprotectin (CP) is a calcium- and zinc-binding protein of the S100 family expressed mainly by neutrophils with important extracellular activity. The aim of the current review is to summarize the latest findings concerning the role of CP in a diverse range of inflammatory and noninflammatory conditions among children. Increasing evidence suggests the implication of CP in the diagnosis, followup, assessment of relapses, and response to treatment in pediatric pathological conditions, such as inflammatory bowel disease, necrotizing enterocolitis, celiac disease, intestinal cystic fibrosis, acute appendicitis, juvenile idiopathic arthritis, Kawasaki disease, polymyositis-dermatomyositis, glomerulonephritis, IgA nephropathy, malaria, HIV infection, hyperzincemia and hypercalprotectinemia, and cancer. Further studies are required to provide insights into the actual role of CP in these pathological processes in pediatrics.