A Quantitative Assessment of Mucosal Eosinophils in the Gastrointestinal Tract of Children Without Detectable Organic Disease

Abstract

Background Accurate measurements of mucosal eosinophil concentrations in gastrointestinal tracts of healthy children are necessary to differentiate health and disease states in general, and better define eosinophilic gastrointestinal diseases. Study We retrospectively reviewed gastrointestinal biopsies from children with macroscopically normal endoscopies, who, after a minimal follow-up of one year, were not diagnosed with any organic disease. Peak eosinophil concentrations and distributions were assessed from each segment of the gastrointestinal tract. Results Three centers (Italy, United Kingdom, and Israel) contributed 202 patients (median age 13 years IQR 9.5–15.5, range 1–18 years). Median (IQR, range) eosinophil concentrations (eos/mm2) were: esophagus 0 (0–0, 0–84), stomach 0 (0–4, 0–84), duodenal bulb 20 (13–30, 7–67), second part of duodenum 20 (13–29, 0–105), terminal ileum 29 (14–51, 0–247), cecum 53 (37–89, 10–232), ascending colon 55 (25–84, 0–236), transverse colon 38 (21–67, 4–181), descending colon 29 (17–59, 0–114), sigmoid colon 25 (13–40, 0–215) and rectum 13 (4–28, 0–152). Significant geographical variance was present, however, no differences in eosinophil concentrations were identified between children with resolving symptoms vs. those with functional diagnoses, nor across age groups. Conclusions Standardized eosinophil concentrations from the gastrointestinal tracts of children without organic disease will serve to better define both health and disease states. No differences were found between resolved symptoms vs. functional diagnoses nor between age groups in this pediatric cohort.

Clinicopathologic Characterization of Lymphocytic Colitis in the Pediatric Population

“…Other previously reported histologic findings include lamina propria eosinophilia (17%) and increased apoptotic bodies (35%), 21 but it is unclear how these two findings were defined. In our cohort, we found the median number of lamina propria eosinophils to be 27 (range: 6–66) which is within the range of expected number of eosinophils in colon biopsy samples from children 56,57 ; more importantly, there were only four cases with eosinophilic cryptitis and none of the biopsies had eosinophilic crypt abscesses.…”

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis

“…While most of these studies used cross‐sectional cohorts of children with obvious functional complaints, in most cases the children were not followed up to ensure that no organic disease developed after endoscopy or that they had no evidence of bacterial ( H pylori infection), parasitic, or systemic disease that might have contributed to the mucosal eosinophilia. Two studies by Hoofien et al (104) and Koutri et al (28) compared children with resolving symptoms with those who had FGIDs, and found no significant differences in peak eosinophil counts. It should be noted however, that other studies have reported higher GI eosinophil counts in the gastric antrum and body of children with FGIDs compared to normal pediatric reference values (24) and in gastric antrum of children with FGIDs compared to healthy controls (25).…”

“…The limitation remains that asymptomatic children were not included for ethical reasons. Both studies (28,104), which were international cohorts from countries in Europe and Israel, but did not include cohorts from North America, found geographic variance in peak eosinophil counts. The geographic differences noted within Europe mean that further differences around the world cannot be ruled out which may be another limitation in setting universal standards.…”

“…We were able to obtain raw data from two large (28,104) and one small (108) study that included pediatric patients who underwent endoscopy for nonspecific functional complaints and were later found to have no organic disease on follow‐up (28,104,108). Using individual patient‐data, we created a single large cohort (n = 143–314 at various anatomic sites) from which the median, IQR, outliers [defined as (upper limit of IQR + 1.5 × IQR) − (upper limit of IQR + 3 × IQR)], and extreme outliers [defined as >(upper limit of IQR + 3 × IQR)] were calculated.…”

“…In contrast to the esophagus, which is normally devoid of eosinophils, eosinophils in the rest of the GI tract are resident mucosal cells. Attempts have been made over several decades to determine eosinophil density in general and peak eosinophil counts in the normal pediatric GI tract (25)(26)(27)(28)30,32,47,49,74,77,(101)(102)(103)(104)(105)(106)(107)(108). However, the studies were subject to several significant limitations.…”