Editor: Deborah Sesok-Pizzini, MD, MBA, adjunct professor, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and vice chair for clinical pathology and transfusion medicine, Nemours Children’s Health, Wilmington, Del.
Diagnostic performance of fecal eosinophil-derived neurotoxin and lipocalin-2 in pediatric IBD
September 2026—Three subtypes of inflammatory bowel disease present as chronic inflammation in children and adolescents: ulcerative colitis, Crohn’s disease, and IBD unclassified. The incidence of IBD continues to increase in pediatric populations, with a growing number of cases in preschool children. Familial patterns have been observed in 19 to 41 percent of patients, especially those younger than 11 years of age. The diagnosis of IBD is typically based on clinical presentation, endoscopic evaluation, and histological assessment of intestinal mucosa. While endoscopy can be used to differentiate between Crohn’s disease and ulcerative colitis, it is an invasive procedure that involves visualizing colonic mucosa. Fecal biomarkers are intended to support the diagnosis of IBD rather than replace endoscopy and histologic examination. Fecal calprotectin (FC), a calcium- and zinc-binding protein that constitutes 50 to 60 percent of neutrophil cytosolic proteins, is a biomarker for neutrophilic infiltration in the gut during inflammatory conditions. The authors identified two other biomarkers for use in IBD screening: eosinophil-derived neurotoxin (EDN), a protein with ribonuclease activity found in eosinophil cytotoxic granules, and lipocalin-2 (LCN-2), which functions as a stable bacteriostatic protein in neutrophil granules. Both have shown increased concentrations in active ulcerative colitis and Crohn’s disease. The authors conducted a study to identify similarities and differences between fecal EDN (fEDN), LCN-2, and FC and determine the advantages and disadvantages of using each one in pediatric IBD screening. They also determined the sensitivity and specificity of fEDN and LCN-2 as stool biomarkers and compared them to FC. The authors performed a case-control study in patients younger than 18 years of age during the six-month period of January through June 2024 at the pediatric gastroenterology unit and GIT (gastrointestinal) endoscopy unit of Beni-Suef (Egypt) University Hospitals. The study included 90 participants who were divided into group one (n = 30, study group), group two (n = 30, healthy group), and group three (n = 30, acute diarrhea group). The study group consisted of 12 IBD patients diagnosed with Crohn’s disease and 18 IBD patients diagnosed with ulcerative colitis based on endoscopic and histological findings. The healthy group comprised age- and sex-matched healthy children with no history of chronic gastrointestinal complaints, who served as controls. The acute diarrhea group comprised age- and sex-matched children presenting with acute diarrhea of fewer than 14 days’ duration. Assessing the acute diarrhea group was critical in determining if the biomarkers were, in fact, representative of more chronic inflammation associated with IBD as opposed to a nonspecific elevation in an acute diarrheal state. Fecal calprotectin, fEDN, and LCN-2 were quantified using a commercially available sandwich ELISA kit. Disease activity was assessed for all IBD patients during the same clinical encounter as stool sample collection. The results showed that mean age, sex, rural residence, consanguinity rates, mode of delivery, and gestational age were not statistically different across all groups. However, breastfeeding was less prevalent (40 percent) among IBD patients than patients with acute diarrhea (60 percent) and healthy controls (73.3 percent). Furthermore, the IBD patients had significantly more siblings (3.03 ± 1.3) than those in the acute diarrhea (2.03 ± 1.1) and healthy control (2 ± 1) groups. With regard to Crohn’s disease and ulcerative colitis in the IBD group, no statistical differences were found across demographics, except for males having a higher percentage of Crohn’s disease (75 percent) and females having a higher percentage of ulcerative colitis (61.1 percent). Analysis of fecal inflammatory markers showed significantly higher levels of all biomarkers in the IBD patients than in the acute diarrhea patients and healthy controls (p<.001). Fecal calprotectin was the only biomarker that differed significantly across the three groups. All three biomarkers distinguished IBD patients from healthy controls: FC with 96.7 percent sensitivity and 93.3 percent specificity (area under the curve [AUC] = 0.98), fEDN with 100 percent sensitivity and 76.6 percent specificity (AUC = 0.95), and LCN-2 with 80 percent sensitivity and 96.7 percent specificity (AUC = 0.9). No statistically significant differences were noted across the three biomarkers in this diagnostic performance comparison. In contrast, the diagnostic accuracy of fEDN was significantly lower than that of LCN-2 and FC in discriminating between IBD and acute diarrhea patients, while FC demonstrated the highest specificity (90 percent) and overall accuracy (AUC = 0.86). Also of note, LCN-2 was the only biomarker to demonstrate a significant correlation with disease duration (r = 0.43, p = .017). The authors concluded that fEDN, LCN-2, and FC were significantly elevated in pediatric IBD patients, with FC showing the strongest diagnostic accuracy for distinguishing IBD patients from those with acute diarrhea. Furthermore, LCN-2 being the only biomarker that correlates with disease duration may support its role in the chronic inflammatory process. These early findings address the utility of the three biomarkers as noninvasive supportive tools for pre-endoscopic assessment of pediatric IBD. However, additional validation via larger prospective multicenter studies is needed to determine if the use of all three combined improves diagnostic accuracy.
Eid RA, Fakhry NA, Ahmed DM, Hodeib M. Diagnostic performance of fecal eosinophil-derived neurotoxin and lipocalin-2 in pediatric inflammatory bowel disease. BMC Gastroenterology. 2026;26:455. doi.org/10.1186/s12876-026-05024-9
Correspondence: Dr. Ragaey Ahmad Eid at ragaeyahmad@med.bsu.edu.eg
ADLM guidance document on incorporating gender diversity into pathology and laboratory medicine
The first published clinical standards of care for the gender-diverse patient population were released in 1979 by the Harry Benjamin International Gender Dysphoria Association, which later became the World Professional Association for Transgender Health (WPATH). The WPATH standards are now in their eighth version. Over the last 15 years, numerous medical societies have published guidelines and recommendations related to clinical care for the gender-diverse patient population, focusing on such subspecialties as endocrinology, pediatrics, plastic surgery, and urology. Efforts have been underway in the United States to provide guidance on handling surgical specimens collected from transgender and intersex patients, as well as for handling specimens arriving with missing or unknown gender or sex markers. However, no U.S. consensus recommendations broadly cover laboratory medicine, anatomic pathology, and pathology informatics. To address the need for pathology guidelines pertaining to the gender-diverse population, an expert panel was convened to review the literature as it relates to clinical and anatomic pathology for this population. The authors, who were panel members and represented a variety of geographically diverse institutions, outlined pathology- and laboratory medicine-specific recommendations for providing optimal care to the gender-diverse population, with a focus on adult-centered care. Panel members met periodically by teleconference and formed subgroups as needed to address specific topics. The guidance document created by the experts reviews evidence for how gender-affirming hormone therapy (GAHT) impacts laboratory tests and the significance of these changes, as well as proposes reference intervals and interpretation for select clinical lab tests for patients on GAHT for six months or longer; discusses transfusion medicine considerations for gender-diverse patient populations; outlines best practices for documenting gender diversity in autopsy and death investigation; summarizes the hormonal and nonhormonal impact of gender-affirming treatment on cytology and histology; and outlines informatics challenges and opportunities for the gender-diverse population with regard to utilizing such measures as fields for sexual orientation/gender identity within electronic health record and laboratory information systems. The experts created a guidance document for interpreting pathology tests for transgender adults while acknowledging that this is an evolving field of medicine. They emphasized the need for a creative, flexible, and patient-centered approach to laboratory testing. Also of importance is customized approaches to laboratory interpretation that include hormonal status, organ inventory, and treatment history. The advancements in guidelines for transgender adults help to reinforce a commitment to health equity in the United States. The authors concluded that ongoing research is needed and should include clinical markers of feminization and masculinization in acute and chronic care settings. In addition, the creation of robust reference ranges with well-defined thresholds tied to clinical outcomes will help in assessing treatment efficacy and providing more personalized patient care.
Thomas TA, Winston-McPherson GN, Amarillo I, et al. ADLM guidance document on incorporating gender diversity in pathology and laboratory medicine. J Appl Lab Med. 2026. doi.org/10.1093/jalm/jfag071
Correspondence: Dr. Matthew Krasowski at matthew-krasowski@uiowa.edu