Intest Res.  2022 Oct;20(4):475-481. 10.5217/ir.2021.00142.

Clinical features of very early-onset inflammatory bowel disease in Japan: a retrospective single-center study

• Usami M
• Takeuchi I
• Kyodo R
• Hirano Y
• Kashiwagi K
• Fujikawa H
• Shimizu H
• Kawai T
• Arai K

• KMID: 2535821
• DOI: http://doi.org/10.5217/ir.2021.00142

Abstract

Background/Aims
Very early-onset inflammatory bowel disease (VEO-IBD), defined as IBD diagnosed in patients younger than 6 years, is a challenge for pediatric gastroenterologists. Although there have been reports regarding VEO-IBD in Western countries, those in Asia are still lacking. This study aimed to investigate the clinical features of Japanese VEO-IBD patients.
Methods
Patients with VEO-IBD diagnosed between 2006 and 2019 were evaluated retrospectively. The disease phenotypes were classified into ulcerative colitis type (UC-type) and Crohn’s disease type (CD-type), and the clinical features and courses were compared between the phenotypes.
Results
Overall, 54 VEO-IBD patients (19 patients with UC-type and 35 patients with CD-type) were evaluated. The median age at onset was 18 months. One patient had severe combined immunodeficiency (SCID), and 9 patients had monogenic IBD. Monogenic IBD was more prevalent in the CD-type patients with perianal disease (CD-type (PD)). The age at onset was significantly lower in the CD-type group (P<0.05). The most common initial symptom was bloody stools (70%), followed by diarrhea (63%), weight loss (24%), fever (20%), and perianal disease (20%). Excluding patients with SCID and monogenic IBD, 23 out of 44 patients (52%) required biologics. The biologics were switched in 11 out of 44 patients (25%), and the majority of these patients (82%) were in the CD-type group. Overall, 9 patients (20%) required intestinal resection or ostomy placement.
Conclusions
CD-type tends to occur at an earlier age, and monogenic IBD occurs significantly more frequently in CD-type (PD). Disease severity and treatment should be individualized, owing to the disease heterogeneity.

Keyword

Monogenic inflammatory bowel disease; Japan; Phenotype; Disease severity; Therapeutics

Figure

• 

  Fig. 1. Age at onset of very early-onset inflammatory bowel disease. (A) Age distribution at onset. (B) Comparison of age at onset between the ulcerative colitis (UC)-type and Crohn’s disease (CD)-type groups. The Mann-Whitney U test is used to assess the differences between the UC-type and CD-type groups.

Reference

1. Benchimol EI, Fortinsky KJ, Gozdyra P, Van den Heuvel M, Van Limbergen J, Griffiths AM. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis. 2011; 17:423–439.

2. Ishige T, Tomomasa T, Takebayashi T, et al. Inflammatory bowel disease in children: epidemiological analysis of the nationwide IBD registry in Japan. J Gastroenterol. 2010; 45:911–917.

3. Martín-de-Carpi J, Rodríguez A, Ramos E, et al. Increasing incidence of pediatric inflammatory bowel disease in Spain (1996-2009): the SPIRIT Registry. Inflamm Bowel Dis. 2013; 19:73–80.

4. Heyman MB, Kirschner BS, Gold BD, et al. Children with early-onset inflammatory bowel disease (IBD): analysis of a pediatric IBD consortium registry. J Pediatr. 2005; 146:35–40.

5. Kammermeier J, Dziubak R, Pescarin M, et al. Phenotypic and genotypic characterisation of inflammatory bowel disease presenting before the age of 2 years. J Crohns Colitis. 2017; 11:60–69.

6. Aloi M, Lionetti P, Barabino A, et al. Phenotype and disease course of early-onset pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2014; 20:597–605.

7. Ledder O, Catto-Smith AG, Oliver MR, Alex G, Cameron DJ, Hardikar W. Clinical patterns and outcome of early-onset inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2014; 59:562–564.

8. Kerur B, Machan JT, Shapiro JM, et al. Biologics delay progression of Crohn’s disease, but not early surgery, in children. Clin Gastroenterol Hepatol. 2018; 16:1467–1473.

9. Oliva-Hemker M, Hutfless S, Al Kazzi ES, et al. Clinical presentation and five-year therapeutic management of very early-onset inflammatory bowel disease in a Large North American Cohort. J Pediatr. 2015; 167:527–532.

10. Kelsen JR, Conrad MA, Dawany N, et al. The unique disease course of children with very early onset-inflammatory bowel disease. Inflamm Bowel Dis. 2020; 26:909–918.

11. Kerur B, Benchimol EI, Fiedler K, et al. natural history ofvery early onset inflammatory bowel disease in North America: a retrospective cohort study. Inflamm Bowel Dis. 2021; 27:295–302.

12. Bequet E, Sarter H, Fumery M, et al. Incidence and phenotype at diagnosis of very-early-onset compared with later-onset paediatric inflammatory bowel disease: a population-based study [1988-2011]. J Crohns Colitis. 2017; 11:519–526.

13. Al-Hussaini A, El Mouzan M, Hasosah M, et al. Clinical pattern of early-onset inflammatory bowel disease in Saudi Arabia: a multicenter national study. Inflamm Bowel Dis. 2016; 22:1961–1970.

14. Fang YH, Luo YY, Yu JD, Lou JG, Chen J. Phenotypic and genotypic characterization of inflammatory bowel disease in children under six years of age in China. World J Gastroenterol. 2018; 24:1035–1045.

15. Arai K, Kunisaki R, Kakuta F, et al. Phenotypic characteristics of pediatric inflammatory bowel disease in Japan: results from a multicenter registry. Intest Res. 2020; 18:412–420.

16. Kudo T, Arai K, Uchida K, et al. Very early-onset inflammatory bowel disease in Japan: a nationwide survey. J Gastroenterol Hepatol. 2021; 36:151–155.

17. Okou DT, Kugathasan S. Role of genetics in pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2014; 20:1878–1884.

18. Levine A, Griffiths A, Markowitz J, et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis. 2011; 17:1314–1321.

19. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013; 48:452–458.

20. van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM. TREC based newborn screening for severe combined immunodeficiency disease: a systematic review. J Clin Immunol. 2015; 35:416–430.

21. Nakagawa N, Imai K, Kanegane H, et al. Quantification of κ-deleting recombination excision circles in Guthrie cards for the identification of early B-cell maturation defects. J Allergy Clin Immunol. 2011; 128:223–225.

22. Kelsen JR, Sullivan KE, Rabizadeh S, et al. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position paper on the evaluation and management for patients with very early-onset inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2020; 70:389–403.