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Three key aspects of pediatric Crohn's disease research you need to know
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Due to the worldwide increase in Crohn’s disease during the past 30 years, especially in pediatric incidence, researchers have developed a better understanding of the disease and more effective treatments.
Here is what you need to know about the changing epidemiology, etiology and treatment options for pediatric Crohn’s disease (CD), according to a review of current research compiled by investigators from the department of pediatrics at the University of Melbourne.
Increased global incidence
Current estimates of Americans and Europeans with CD are 700,000 and 1 million, respectively. Long presumed to be a Western disease, incidence appears to be increasing in developing regions of Asia, Eastern Europe and South America, particularly in pediatric CD. With estimates of a 10- to 20-fold rise over 30 years, increases in pediatric CD have been confirmed in Australia, Scotland, Sweden, Czechoslovakia, the United Kingdom and Shanghai. Fifteen percent to 25% of CD patients’ initial symptoms present in childhood (mean age, 11 years).
Current theories of causation
Environmental factors
“It is currently believed that CD occurs as part of an interplay between environmental and immunological factors in a genetically susceptible host,” the researchers wrote. Some evidence suggests that environmental risk factors in childhood like improved hygiene, urban residence or relocation to regions with high incidence may outweigh genetic factors in developing CD. The hygiene hypothesis proposes that childhood pathogen and immunological stimuli exposure may protect against CD.
Genetic susceptibility
Studies have indicated several genetic markers that may increase CD risk, including the NOD2 gene that regulates immune response to bacteria. Defects in autophagy, the genetic process linked to NOD2 and other genes, may affect immune response to pathogens and contribute to CD risk.
Microbial triggers
Recent advances in metagenomics have provided data that point to dysbiosis of gut microbiota as the key source for causation. Such studies indicate a general reduction in bacterial diversity in the gut of CD patients. Another area of exploration is the impact of bacteriophages on gut function, but evidence is currently lacking. A number of specific transmissible agents also have been proposed as causal of CD, the most well-known is paratuberculosis, an infection that causes bovine bowel disease. It has been identified in up to 50% of children with new CD diagnoses, but researchers remain unsure of its implication in humans.
Current and emerging therapies
5-ASA
First-line symptom management therapies are typically 5-aminosalicylic acid (5-ASA)-based combinations, including sulfasalazine and mesalamine, but there is conflicting evidence for their efficacy in inducing remission.
Corticosteroids
First-line treatments to induce remission are usually prednisolone and its equivalents, with up to 90% response rates. Concerns include risk for infection, growth and bone health. Budesonide is associated with fewer side effects and less adrenal suppression than prednisolone and may be a potential alternative for children, according to some data.
Exclusive enteral nutrition
Multiple studies have shown exclusive enteral nutrition safely and effectively induces remission without the side effects associated with corticosteroids. Despite its efficacy and safety profile, however, it is underutilized due to poor perception, lack of experience and difficulty associated with the treatment, especially unpalatable formulas and possible need for an enteral tube.
Immunomodulators
The most widely used immunomodulators for induction and maintenance therapy are the thiopurines azathioprine (AZA) and 6-mercaptopurine (6-M), but methotrexate (MTX) use is increasing. AZA and 6-M are effective in combination with corticosteroids, and guidelines suggest similar efficacy of MTX, but evidence is limited. Immunomodulators are increasingly used as a primary treatment for severe disease, especially in pediatric patients.
Biologics
Biologics, including infliximab, adalimumab and certolizumab, target molecules and pathways involved in the inflammatory process. Infliximab has transformed CD treatment, and is used to induce remission and as a maintenance therapy. Severe infections are a risk factor, but the same collective risks associated with narcotic analgesics and steroids are greater.
Disclosure: Researcher Anthony G. Catto-Smith, MD, has received speaker’s fees from Janssen and honoraria as a member of advisory boards.
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