Children & teens with IBD: not simply little adults (Part 1)

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Dr Richard Russell

Consultant Paediatric Gastroenterologist
Yorkhill Hospital
Glasgow, Scotland

 

Paediatric inflammatory bowel disease (IBD), comprising paediatric Crohn’s disease (PCD) and paediatric ulcerative colitis (PUC), is increasingly being recognised in children and teenagers,1 necessitating comprehensive management to ensure physical and psychosocial wellbeing.

While adult UC and CD tend to occur at a similar frequency, PCD is much more common than PUC. Phenotypically, paediatric IBD is associated with more extensive disease than adult IBD.2 Children with CD undergo more surgeries than their UC counterparts due to the more extensive nature of their disease. PCD is associated with greater disease activity than adult-onset CD.3

Children are not just ‘small adults’ and consideration must be given to these distinguishing features between early onset and adult onset IBD alongside additional issues of growth, puberty, psychosocial problems and treatment compliance. Consequently, distinct approaches in the management of IBD between both populations are warranted.

During a recent visit to Australia, Dr Richard Russell shared his clinical expertise with local specialists on the salient differences between managing adult and paediatric IBD.

Aetiology of paediatric IBD: what’s new?

Akin to adult onset IBD, the underlying pathogenesis of paediatric IBD involves a complex interaction of genetic, environmental and immune factors. The microbiome, in particular, is pivotal. Evidence has been growing that commensal gut flora is linked with IBD. However, studying the microbiome is challenging as bacterial loads vary by geographical locations and are altered by treatment.

Bacterial manipulation is being investigated as a treatment option using EEN, antibiotics, faecal transplants, new drug pathways and pharmacogenomic studies. Interestingly, bacterial diversity is decreased in CD but not UC.

To date, treatments investigating the manipulation of the microbiome using prebiotics or probiotics have not been proven to work. The role of antibiotics in pregnancy and early childhood is being studied – early data suggests that exposure to antibiotics in the first few years of life may increase the risk of IBD.4

Diagnosing paediatric CD: pointers for practice

  • Always perform a colonoscopy and gastroscopy (top and tail) in children suspected to have IBD – 60–70% of them will have CD.5
  • Magnetic resonance imaging (MRI) is now standard of care for detecting small bowel disease – patients tend to prefer MR enterography over enteroclysis but this is not appropriate for children under 8 years.
  • Larger-sized adolescents may benefit from being seen by a radiographer who treats adults.
  • The Paediatric Ulcerative Colitis Activity Index (PUCAI) is a well-validated assessment for paediatric UC that has also been validated in adults.6 It can be done quickly and helps risk-stratify patients to determine optimal therapy. It is especially useful in acute severe disease. The Paediatric Crohn’s Disease Activity Index (PCDAI) is also useful; however, it has its limitations and will not always be high in the presence of severe disease.

Treating paediatric Crohn’s disease

Due to the limited number of treatment options available, it is important to maximise each agent to its most effective dose before moving on to the next therapy. However, move quickly to add further therapies in patients who fail on existing drugs.

Existing treatment options are as follows:

Exclusive enteral nutrition (EEN)7-12

  • EEN is only effective in paediatric CD, not paediatric UC. It should be used as a preferred 1st-line induction therapy in paediatric CD (all locations) over steroids.7
  • Both EEN and steroids increase weight but the former increases lean muscle mass while the latter, primarily fat.8,9 EN alone does not increase height (z-score) in the medium term.
  • EEN has been proven to be effective in 80% of paediatric CD patients – treatment achieves mucosal healing after 8 weeks of treatment with minimal side effects.7,10,11
  • EEN also alters gut pH and bacterial composition;12 decreasing faecal calprotectin and C-reactive protein levels.

Steroids13

  • Steroid use in children may pose significant side effects, particularly in steroid-dependent patients.
  • Steroids should not be used in combination with EEN as the former increases appetite and there is no evidence of increased efficacy with combination therapy.
  • Limit steroid doses generally to 1 mg/kg (max. 40–60 mg/day depending on institution protocol), tapering treatment over time.

Immunomodulators13,14

  • AZA is used as first-line immunosuppression13
  • Optimise dose of TP but continue to monitor LFTs and risk of myelosuppression.
  • Consider MTX, REMICADE® (infliximab) or surgery for TP failure.

Biologics13-18

  • Overall, adolescents require more biologic therapy than adults as they present with a more aggressive extensive phenotype.14
  • REMICADE® has proven effective in the majority of patients with paediatric CD15 – primary non-response is uncommon.
  • Individualised treatment by body weight is recommended.15,16
  • Patient preference for IV infusions over SC injections may relate to convenience (i.e. dosing frequency). Involving patients in decision making regarding route of administration may improve compliance.17
  • REMICADE® is the only biologic to demonstrate improved height (z-score) and bone health with treatment.15,18
  • Treatment cessation: In Dr Russell’s experience, only 20% of patients are eligible to stop REMICADE® therapy using the criteria outlined in the STORI study, of which about half will relapse and require a re-start. Also in keeping with the style of the STORI study, resume with maintenance treatment, not re-induction to reduce the risk of infusion reactions. Perform calprotectin tests 3-monthly in patients to detect sub-clinical information prior to relapse.19

AZA, azathioprine; 6-MP, 6-mercaptopurine; TP, thiopurine; LFT, live function test; MTX, methotrexate

Treating paediatric ulcerative colitis

  • In Australia, sulphasalazine is the first 5-ASA that is used (under PBS requirements). However, it is associated with a number of side effects and poor compliance by patients due to the need for multiple daily doses.20
  • Global data indicate a high rate (~30%) of acute severe UC (ASUC) in children. Intravenous steroids are standard treatment in ASUC – after day 5 of treatment, rescue therapy or surgery should be introduced using the PUCAI as an assessment guide if there has not been a significant response to steroid treatment.21
  • While children with UC are generally predisposed to developing colorectal cancer later in life, improved treatment strategies to reduce inflammation may attenuate this risk.

Risky business: communicating treatment risks effectively to IBD patients

  • It is usually best to discuss the benefits of treatment first.
  • Frame the issues associated with a lack of treatment and the risk of disease.
  • Outline the risk of developing drug-related side effects – try and contextualise statistics as far as possible e.g. describe the risk of developing lymphoma with immunosuppressant or biologic therapy versus the general population.
  • Always be truthful to build trust in the doctor-patient relationship.
  • Use written consent where appropriate to demonstrate that treatment benefits and risks have been discussed with the patient/parent.

Handy hint: Children, especially adolescents, may not directly interact as much with their healthcare providers. For additional support, try using electronic contact.

Please note, the views expressed in this article are not necessarily those of the sponsor.

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References

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  16. Crohn’s & Colitis Foundation of America. Treating children and adolescents, available at www. ccfa.org/resources/treating-children.html (accessed 16 October 2013).
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