Tag Archives: early onset inflammatory bowel disease

Infliximab -Low Response in Young Kids (7 years and younger) with IBD

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 JPGN 2014; 59: 758-62. The full abstract for this reference follows but the message from this retrospective study of 33 children is clear –a much smaller percentage of the youngest children respond to infliximab compared to older children, adolescents and adults. In the discussion, the authors note that younger children may need higher dosing to maintain good infliximab levels or the disease pathogenesis may be much different (eg. underlying immunodeficiency and different gene mutations).

Here’s the abstract (from JPGN twitter feed):

Background: Infliximab (IFX) is efficacious for induction and maintenance of remission in pediatric patients with moderate-to-severe inflammatory bowel disease (IBD). It has, however, not been studied in patients 7 years old and younger. Our aim was to characterize efficacy and safety of IFX therapy in this cohort.

Methods: This was a retrospective study of patients with IBD ages 7 years and younger, treated with IFX between 1999 and 2011. Medical records were reviewed for age of diagnosis, disease phenotype, therapy, surgery, IFX infusion dates, dose, and intervals. Outcome measures included physician global assessment, corticosteroid requirement, and adverse events.

Results: Thirty-three children (ages 2.4–7 years) were included. Twenty patients had Crohn disease, 4 had ulcerative colitis, and 9 had indeterminate colitis. Maintenance of IFX therapy at 1, 2, and 3 years was 36%, 18%, and 12%, respectively. Patients of age 5 years and younger had the lowest rates of maintenance of therapy at 25% at year 1, and 10% at years 2 and 3 combined. Nine percent of all of the patients demonstrated response measured by the physician global assessment and were steroid free at 1 year. There were 8 infusion reactions. There were no malignancies, serious infections, or deaths.

Conclusions: IFX demonstrated a modest response rate and a low steroid-sparing effect in patients with IBD 7 years old and younger. Although this is a limited study, there appears to be a trend for decreased sustained efficacy with IFX in this age group, particularly in children 5 years old and younger, when compared with the previously published literature in older children.

Link to NASPGHAN Lectures and Postgraduate Course

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Later this week, our national pediatric GI meeting (North American Society for Pediatric Gastroenterology Hepatology and Nutrition) is starting in Atlanta.  Many in my group are involved and presenting.

The following link (with permission from NASPGHAN) is to the website with links to all of these lectures:

NASPGHAN 2014 Atlanta meeting

For those interested only in the Syllabus for the Postgraduate Course:  NASPGHAN 2014 Postgraduate Course.

Topics include in this 200 page (online) book: primary sclerosing cholangitis, jaundiced infant, acute liver failure, “dreaded” endoscopy wake up calls, endoscopy for biliary tract disease, extraesophageal manifestations of gastroesophageal reflux, constipation, eosinophilic esophagitis, motility disorders, FODMAPs diet, nutrition for neurologically impaired, early onset inflammatory bowel disease, “luminitis” due to non-IBD causes, new IBD treatments, and diet-microbiome.

Should be great!

Also, to plan your meeting -go to NASPGHAN home page and use mobile guidebook: NASPGHAN 2014 has gone mobile using Guidebook!

More Data on Early-Onset Pediatric Inflammatory Bowel Disease

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In 2009, a large prospective database involving Italian Pediatric Gastroenterologists was established.  A recent study describes the classification (Paris) and phenotype of early-onset pediatric inflammatory bowel disease (EO-IBD) (Inflamm Bowel Dis 2014; 20: 597-605).

In 506 consecutive patients, 224 had Crohn’s disease (CD), 245 ulcerative colitis (UC) and 37 IBD-unclassified.

Key findings:

  • 11% were aged 0-5 years, 39% 6-11 years, 50% were 12-18 years.
  • UC was more frequently diagnosed in 0-11 years of age whereas as CD was more common in 12-18 years.
  • EO-Crohn’s showed more frequent isolated colonic disease
  • EO-UC noted 62% with pancolitis compared with 38% in 6-11 years and 31% in 12-18 year group

Take-home message: The authors conclude that “EO-IBD exhibits an extensive phenotype and benefit from aggressive treatment strategies, although surgical risk is similar to later-onset disease. A family history for IBD is not common in EO disease.”

IL-10 and early onset IBD

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Among physicians who take care of patients with inflammatory bowel disease (IBD), there is an understanding that the labels “Crohn’s disease” (CD) and “ulcerative colitis” (UC) are imprecise labels.  There may be many subtypes of IBD that are classified as CD or UC.  This is becoming even more clear with advances in genetics which have shown specific genetic defects that predispose to an IBD phenotype.  In fact, more than 100 genetic loci have been uncovered that contribute to IBD, more than any other complex disease (according to editorial in same issue as reference below, pgs 285-87).

Immunodeficiency disorders, like chronic granulomatous disease, are well-recognized as potential mimics for IBD. More recently, IL-10 and IL-10 recpetor genetic mutations have been associated with early-onset IBD phenotypes (Gastroenterol 2012; 143: 347-55.)

In this study, 66 patients whose IBD started before age 5 were investigated for mutatons in the genes encoding IL-10, IL10R1, and IL-10R2.  IL-10R deficiency was confirmed with functional assays of patients’ mononuclear cells.  “Using a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency.”  In all 16 patients, the phenotype included refractory colitis with perianal disease; symptoms developed in the first three months of life in these 16 patients.  Five of these patients improved after hematopoietic stem cell transplantation with a median followup of 2 years.

Take-home message:

Test patients with infantile IBD for IL-10 and IL-10 receptor deficiency

Contact for IL-10 testing (free):

Karoline Fiedler, Clinical Research Coordinator, IBD Program, Toronto

karoline.fiedler@sickkids.ca

http://www.neopics.com

Crohn’s disease Differential Diagnosis:

  • Tuberculosis
  • Histoplasma
  • Sarcoidosis
  • Amebiasis
  • CMV
  • C. diff
  • Klebsiella oxytoca
  • Actinomycosis
  • Vasculitis (dermatomyositis, Wegener’s, SLE)
  • FMF
  • Allergic colitis
  • Hirschsprung’s
  • Autoimmune enteropathy
  • HIV
  • Chronic granulomatous disease
  • Glycogen storage dz, 1B
  • Hermansky-Pudlak syndrome
  • Wiskott Aldrich syndrome
  • NEMO (NF-kB essential modifier) deficiency
  • Leukocyte adhesion deficiency
  • SCID
  • Behcet’s
  • FELS/hemophagocytic lymphohistiocytosis
  • Typhlitis
  • HSP
  • Solitary rectal ulcer syndrome
  • Early-onset: IL10/IL10R deficiency, XIAP, ADAM17, NCF2 gene variant

Additional references:

  • -Gastroenterol 2012; 143: 347-55.  IL-10 signaling defects and IBD.
  • -Gut 2012; 61: 1028-35.  NCF2 gene variant and IBD.
  • -NEJM 2011; 365: 1502-408.  ADAM17 deletion and IBD.
  • -NEJM 2009; 361: 2033-45.  IL-10 receptor and IBD.
  • -JPGN 2010; 51: 690.  Discusses sarcoid (check angiotensin converting enzyme, CGD, Hermansky Pudlak)
  • -JPGN 2010; 50: 99.  Perianal dz in young children may be due to autoimmune neutropenia. -IBD 2008; 14: 1443.  phagocyte dysfunction.  Also, discusses Hermansky-Pudlak, GSD 1B, chronic granulomatous disease, Chediak-Higashi, leukocyte adhesion deficiency, cylic neutropenia, congenital neutropenia
  • -Clin Gastro & Hep 2009; 7: 1037.  MRI best study for perianal fistulas.
  • -JPGN 2006; 42: 405.  Vasculitis mimicking IBD.
  • -Pediatr 2008; 121:  447.  Consider chronic granulomatous disease -particularly if recurrent.  15-18% of CGD pts with perianal abscess.  Immunocompromised hosts at increased risk along with Crohn’s patients.  However, “vast majority” do not have underlying disease.  Can treat perianal abscess medicaly in otherwise healthy infants. (Peds 2007; 120: e548).  www.pediatrics.org/cgi/content/full/120/3/e548
  • -NEJM 2005; 352: 489-94.
  • -Gold B et al. NEJM 2003; 349 (26): 2541, Table 2

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