29April2021

Histopathological diagnosis of paediatric-onset IBD

Pamela Baldin, H-ECCO Member

Pamela Baldin
© ECCO

Paediatric-onset Inflammatory Bowel Diseases (IBDs) represent about 25%–30% of all IBDs. As in adult patients, cases are classified as Ulcerative Colitis (UC) or Crohn’s Disease (CD). In addition, a third diagnostic category, unclassified-IBD (U-IBD), can be used when a definite differential diagnosis between UC and CD is not possible.

Paediatric-onset IBDs, by definition, are those IBDs which are diagnosed in children and adolescents under the age of 17 years. They are further categorised as very early onset IBD (VEO-IBD) when the disease is diagnosed before 6 years of age, infantile IBD when the diagnosis is made before 2 years of age and neonatal-onset IBD when the patient is 28 days old or less. 

The histological diagnosis of paediatric-onset IBDs can be difficult since paediatric IBDs may show atypical microscopic findings, especially at the onset of disease. For this reason, a multidisciplinary approach is essential in order to make an accurate diagnosis. The pathologist, while analysing the glass slide, should take into consideration all clinical, endoscopic, radiological, and serological parameters which are of paramount importance. If this information is not available, a discussion with the clinicians or surgeons is a must. Moreover, consideration of the whole clinical context is useful to rule out other possible differential diagnoses, such as infectious diseases, allergic diseases and primary immunodeficiency disorders.

In 2014, ESPGHAN (European Society of Paediatric Gastroenterology, Hepatology and Nutrition) published consensus-based guidelines for the diagnosis of paediatric IBDs; the guidelines also included the histopathological features of paediatric IBDs (1, 2).

For the diagnosis of UC, the main pathological feature is the continuous colonic mucosal inflammation starting from the rectum and without small bowel involvement. Usually, the disease is worse distally. Crypt architectural alterations, such as crypt distortion and decreased crypt density, along with basal plasmacytosis, are considered features of chronicity and can occur in around 70% of patients; they may also be accompanied by cryptitis or crypt abscesses. Furthermore, goblet cell mucin depletion and Paneth cell metaplasia may be found.

Paediatric UC includes some atypical clinical and morphological features (3) such as rectal sparing (reported in 5%–30% of patients), lack of architectural distortion in biopsies taken during the early onset of symptoms (reported in up to 34% of the patients), caecal patch, which is the presence of caecal and peri-appendiceal inflammation, mild ulceration, transmural inflammation and deep ulcers in patients with severe disease. Upper gastrointestinal tract involvement, previously considered to be a finding specific to CD, may be seen in UC, especially in the form of gastric microscopic involvement (4). It is also reported that one-third of UC patients with pancolitis show backwash ileitis.

As regards paediatric CD, the key pathological feature is segmental and transmural inflammation that is usually more intense proximally, with variable rectal involvement. The presence of non-caseating granulomas is more frequent in paediatric CD than in adult CD and is reported in around 20% of biopsies and 50% of surgical specimens. The ileum and the small intestine are often involved, and the upper gastro-intestinal tract is more commonly affected than in adult patients (5).

In some cases, despite the correlation with the clinical and radiological features, it is not possible to accurately differentiate between UC and CD. For these cases the diagnosis of IBD-U should be used until the disease develops more characteristic features and can be better classified. In the literature, IBD-U is diagnosed in around 22% of patients younger than 8 years old; this percentage decreases for older patients.

The pathogenesis of paediatric-onset IBDs is not completely understood. Multiple environmental, immune and genetic factors appear to be involved.

The genetic contribution seems to be polygenic and involves over 300 genes. However, in a subset of VEO-IBD patients, a monogenic or digenic defect has been identified. It can involve genes related to primary immunodeficiencies and several mechanisms related to intestinal immune homeostasis (6). These cases are categorised as monogenic IBD. Patients with monogenic IBD seem to have more severe disease and usually respond poorly to conventional immunosuppressive therapy.

There is a lack of specific criteria or features for the histological diagnosis of monogenic IBD; nonetheless, there are some histopathological findings suggestive of immune dysregulation, for instance, epithelial cell apoptosis with crypt dropout, epithelial shedding, tufting, villous blunting and marked eosinophilia. These features, when present, may raise the suspicion of monogenic IBD (7).

In conclusion, the main histopathological characteristics of paediatric IBDs are similar to those of adult-onset IBD. However, paediatric patients may present with atypical and overlapping features that can make the diagnosis and classification of IBD difficult not only for clinicians but also for pathologists.

Pathologists need to be aware of these ambiguous clinical scenarios while evaluating IBD samples of paediatric patients. It is also important to have a multidisciplinary approach in order to provide an accurate diagnosis and improve patient care.

References

  1. Levine A, Koletzko S, Turner D, et al.  European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. ESPGHAN revised Porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J. Pediatr Gastroenterol Nutr. 2014;58:795–806.
  2. Van Rheenen PF, Aloi M, Assa A, et al. The medical management of paediatric Crohn's disease: an ECCO-ESPGHAN guideline update. J Crohns Colitis. 2020;7:jjaa161.
  3. Bousvaros A, Antonioli D, Colletti R, et al.  Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America. J Pediatr Gastroenterol Nutr. 2007;44:653–74.
  4. Abuquteish D, Putra J. Upper gastrointestinal tract involvement of pediatric inflammatory bowel disease: A pathological review. World J Gastroenterol. 2019;25:1928–35.
  5. Levine A. Pediatric inflammatory bowel disease: is it different? Dig Dis. 2009;27:212–4.
  6. Nameirakpam J, Rikhi R, Rawat SS, Sharma J, Suri D. Genetics on early onset inflammatory bowel diseases: An update. Genes Dis. 2019;7:93–106.
  7. Conrad MA, Carreon CK, Dawany N, Russo P, Kelsen JR. Distinct histopathological features at diagnosis of very early onset inflammatory bowel disease. J Crohns Colitis. 2019;13:615–25.

Posted in ECCO News, Committee News, Volume 16, Issue 2, H-ECCO

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