IBD Shorts: September 2019

S Olivia et al (including Stanley Cohen from GI Care for Kids) Clin Gastroenterol Hepatol 2019; 17: 2060-7.A Treat to Target Strategy Using Panenteric Capsule Endoscopy in Pediatric Patients with Crohn’s Disease”  In this prospective study with 48 children with Crohn’s disease, pan-enteric capsule endoscopy (PCE) detected inflammation in 34 (71%) at baseline, 22 (46%) at week 24, and 18 (39%) at week 52.  PCE results were used to manage treatment and resulted in change in therapy in 71% at baseline and 23% at week 24.  Furthermore, PCE increased the proportions of patients in deep remission, up to 58% at week 52.

M Wright, et al. J Pediatr 2019; 210: 220-5. This case report of a 4 year-old boy with a perianal abscess and granulomatous colitis identified a NCF4 mutation causing severe neutrophil dysfunction.  He developed osteomyelitis with anti-TNF therapy and did not respond to vedolizumab. He had an excellent outcome following a hematopoietic stem cell transplantation. This study reinforces the potential benefit of investigating VEO-IBD which could allow more targeted therapy. Related blog post:

P Zapater et al. Inflamm Bowel Dis 2019; 25: 1357-66. This study with 112 patients with Crohn’s disease showed that serum interleukin-10 levels were directly related to infliximab and adalimumab levels.  This suggests that serum anti-TNF levels are significantly influenced by immunological activation.

JE Axelrad et al. Clin Gastroenterol Hepatol 2019; 17: 1311-22.  This study, using the Swedish National Patient Register, showed that gastrointestinal infection increased the odds of developing IBD in a nationwide case-control study.  “Of the patients with IBD, 3105 (7%) had a record of previous gastroenteritis compared with 17,685 control subjects (4.1%). IBD cases had higher odds for an antecedent episode of gastrointestinal infection (aOR 1.64), bacterial gastrointestinal infection (aOR 2.02) and viral gastrointestinal infection (aOR 1.55)…a previous episode of gastroenteriitis remained associated with odds for IBD more than 10 years later (aOR 1.26).”  The authors note that they cannot formally exclude misclassification bias, but it appears that enteric infections contribute to the development of IBD in susceptible individuals.

Vaccine for Celiac Disease

A recent study (KM Kemppainen et al. Clin Gastroenterol Hepatol 2017; 15: 694-702, editorial 703-5) showed that gastrointestinal infections can trigger celiac disease (CD) and that immunization with the rotavirus vaccine was protective against developing CD.

This study is part of the TEDDY study: The Environmental Determinants of Diabetes in the Young.  The TEDDY cohort involves more than 8000 children who are part of an international prospective cohort who carry genes (HLA-DR-DQ genotypes) with increased risk for diabetes and CD. In this particular group, the authors identified 6327 children who were 4 yrs old by March 2015.

Key Definition: CD autoimmunity (CDA) -children who tested positive for tTG IgA at their annual visit and remained persistently positive 3 months later

Key Findings:

  • Gastointestinal infections (n=13,881) but not respiratory infections (n=79,816) were associated with an increased risk of CDA.  CDA risk was increased within the 3 months of the GI infection.
  • 732 of 6327 (11.6%) developed CDA.  In this cohort, 318 underwent duodenal biopsy and 283 (90%) had biopsy indicative of CD (Marsh score >1). Thus, in their cohort, there is variability in the onset of CD from the onset of CDA.
  • Risk of CDA was reduced in children vaccinated against rotavirus and introduced to gluten before age 6 months (HR =0.57).
  • The exact risk depending on interaction with multiple factors including breastfeeding, HLA genotype, seasonality of birth, and timing of gluten introduction. Timing of infection plays a role as well, as earlier exposure to GI infections earlier in life was associated with a decreased risk of celiac disease.

This reference should be kept handy for vaccine advocates.  Not only can vaccines prevent infections, but they have now been shown to prevent an autoimmune disease (CD).  In addition, previous studies have shown that vaccines can prevent cancers, including hepatocellular carcinoma and cervical cancer.

My take (modified from editorial): This study “demonstrates the power of rigorously conducted prospective studies to reveal complex interactions among genetic and environmental factors.” In addition, this study shows that preventing rotavirus infection with vaccination lowers the risk of celiac disease.

Related blog posts:

SuperPoopers CCFA Team 2017