Distinct Histopathological Features at Diagnosis of Very Early Onset Inflammatory Bowel Disease

Abstract

Background and Aims: Children with very early onset inflammatory bowel disease [VEO-IBD] represent a unique cohort, often with a severe phenotype that is refractory to conventional medications, and some cases have underlying primary immunodeficiencies. Previous work has identified distinct histopathological patterns in the gastrointestinal tract in patients with primary immunodeficiencies. The aim of this study is to characterise the diagnostic histological findings in patients with VEO-IBD as compared with older onset paediatric IBD, and determine if there are unique pathological changes that can shed light on the driving forces of the disease, particularly immunodeficiencies. Methods: Clinical retrospective chart review, including disease characteristics and endoscopic findings, was performed on all included subjects. Two paediatric pathologists reviewed biopsies from diagnostic upper endoscopies and colonoscopies of subjects with very early onset inflammatory bowel disease and older onset inflammatory bowel disease, to evaluate for the presence of 11 histological features previously associated with inflammatory bowel disease and primary immunodeficiencies. Results: The diagnostic gastrointestinal biopsies of subjects with very early onset inflammatory bowel disease differed from those in older onset paediatric IBD, demonstrated by increased frequency of apoptosis, severe chronic architectural changes, small intestine villous blunting, and eosinophils in the crypts, lamina propria, and surface epithelium. Conclusions:The diagnostic biopsies of children with very early onset inflammatory bowel disease can identify characteristic features that may be important in guiding the diagnostic work-up in this population.

Fecal Eosinophil Cationic Protein Is a Diagnostic and Predictive Biomarker in Young Adults with Inflammatory Bowel Disease

“…The reasons why eosinophils seem to be more active in younger patients and also during remission are not known and, as yet, have been largely uninvestigated. It has been reported that colonic eosinophilia is more prevalent in younger than in older children diagnosed with IBD or other colonic diseases [45,46]. Furthermore, tissue eosinophilia seems to be a dominant feature of subclinical histological inflammation for patients with IBD in remission [47], which might be more prevalent in young patients with IBD.…”

“…Clinical follow-up data was available for 202/212 visits (95.3%) of patients with IBD. The median (IQR) follow-up time was 48 (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54) months. The total event rate was 94/202 (46.5%).…”

Lymphocytic Colitis With Increased Apoptosis: A Marker of Mutation in T-Cell-Mediated Immunity?

“…Classic IBD shows granulomas and fissures in Crohn's disease, and crypt abscesses, glandular architectural distortion, and pseudo polyps in ulcerative colitis. 15 Apoptosis is a key feature in VEO-IBD 16 and STAT3 and CTLA-4 mutations have been described as monogenic causes of VEO-IBD. 15 Clinically, VEO-IBD occurs in children younger than 6 years (3 of our 4 patients are older), and histopathologically, in addition to apoptosis, there is generally significant eosinophilia (including eosinophilic crypt microabscesses) and to a lesser extent villous blunting.…”

Inducible Nitric Oxide Regulates Na-Glucose Co-Transport in a Spontaneous SAMP1/YitFc Mouse Model of Chronic Ileitis

“…IBD, consisting of Crohn’s disease and ulcerative colitis, afflicts more than 3.5 million patients in the Western hemisphere with increasing incidence over the last five decades [ 3 ]. IBD is characterized by chronic, unrelenting intestinal inflammation, villus blunting and crypt hypertrophy that leads to malabsorption of fluid, electrolytes and nutrients as well as secretion of fluid and electrolytes [ 28 , 29 , 30 , 31 , 32 ]. This in IBD results in its most common and disabling symptoms, diarrhea, malnutrition, weight loss and in the pediatric population, a failure to thrive.…”