Pattern-based Histologic Approach in Very Early Onset IBD: Main Features and Differential Diagnosis

Abstract

Very early onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella classification composed of IBD-like diseases encompassing both classic IBD (Crohn's disease and ulcerative colitis) and monogenic disorder, both arising before 6 years of age. VEO-IBD patients present significant clinical differences from IBD occurring in older children and in adults, including more severe disease, often unresponsive to conventional IBD therapy and a greater proportion of cases featuring an underlying genetic alteration. Histologic findings of gastrointestinal biopsies can show an IBD-like pattern (both Crohn's disease-like and ulcerative colitis-like pattern), an apoptotic-like and enterocolitis-like pattern. Findings of specific morphologic alterations, such as villous blunting, apoptosis, dense eosinophilic infiltrates, lack of plasma cells and severe glandular atrophy, can suggest a monogenic disorder. Moreover, individuals with monogenic disorders may develop significant problems such as primary immunodeficiency, impacting treatment options. Finally, IBD histology in childhood can differ from that in older patients and adults. This complexity makes a differential diagnosis between IBD and other pediatric diseases involving the gastrointestinal tract difficult, especially considering that histologic features can be similar between different diseases. Without an appropriate diagnosis, the clinical course of VEO-IBD has greater potential for escalated treatment regimens involving extensive surgery and more intensive medical therapies rather than specific therapy directed toward the underlying defect. For these reasons, a patternbased histologic approach correlated with clinical and laboratory findings with a multidisciplinary approach is fundamental to reach a correct diagnosis in an adequate clinical context.

Reply to: A Pattern-based Approach and Multidisciplinary Discussion Are Fundamental for Diagnosis in Very Early Onset Inflammatory Bowel Disease (VEO-IBD)

“…Third, a broad pattern-based approach to VEO-IBD pathology, drawing on data from numerous case reports and small series, is likely the most specific description possible at this time given the paucity of large cohorts with detailed genotype/phenotype/histology correlation. Although Parente et al’s2 set of histologic patterns differ slightly from ours, their approach and rationale appear similar.…”

“…1 We also thank Professor Grillo and his colleagues for their comments on our review of the pathology of very early onset inflammatory bowel disease (VEO-IBD), in light of their recent publications in this area. 2,3 It is reassuring that we are in broad agreement on a variety of issues regarding clinical management of patients with VEO-IBD and the research approach to this cohort, a few of which we would like to elaborate on below.…”

A Pattern-based Approach and Multidisciplinary Discussion Are Fundamental for Diagnosis in Very Early Onset Inflammatory Bowel Disease (VEO-IBD)

“…In particular, we have some comments on the highly challenging topic of very early-onset inflammatory bowel disease (VEO-IBD), which is receiving much attention in the pathology community, and indeed in this journal. Both Wilkins et al’s,2 and our contribution,3 underline the importance of a pattern-based histologic approach to the reporting of VEO-IBD.…”

“…VEO-IBD may show both IBD-like histologic patterns, usually described in older children/adults, as well as non-IBD-like histologic patterns, such as increased crypt apoptoses (apoptotic pattern), active colitis without chronic damage (enterocolitis-like pattern), increased eosinophils or intraepithelial lymphocytes, granulomas and small bowel villous blunting, as previously described 2,3,7,8. Unfortunately, none of the above mentioned characteristics are pathognomonic of a monogenic disorder as they have also been identified in nonmonogenic VEO-IBD.…”

Application of a pattern‐based approach to histological diagnosis in very early onset IBD (VEO‐IBD) in a multicentric cohort of children with emphasis on monogenic disease with IBD‐like morphology

“…4 Unfortunately, histological features in GI biopsy samples from children with MD can overlap with true IBD and various other conditions. [5][6][7][8][9][10] Erroneously labelling the process as 'IBD' in the histology report early in the disease course will prevent the physician from considering further conditions as well as initiating inappropriate clinical management and therapy. 11 Moreover, lesions such as colitis without chronic damage, with eosinophilic-rich inflammation or apoptotic bodies, usually observed in infections, autoimmune disorders, allergic and/or food intolerance, have also been described in MDs.…”