Overview
Definition:
Inflammatory bowel disease (IBD) in pediatrics encompasses chronic, relapsing inflammatory conditions of the gastrointestinal tract, primarily Crohn's disease (CD) and ulcerative colitis (UC)
These conditions are characterized by immune dysregulation leading to transmural inflammation (CD) or mucosal inflammation (UC).
Epidemiology:
The incidence of pediatric IBD is increasing globally, including in India
While historically more prevalent in Western countries, a rising trend is observed in developing nations
Peak onset occurs in adolescence, but it can affect children of any age
Genetics, environmental factors, and gut microbiome alterations are implicated in pathogenesis.
Clinical Significance:
Pediatric IBD significantly impacts a child's growth, development, quality of life, and academic performance
Early and effective management is crucial to induce remission and maintain it, preventing complications such as strictures, fistulas, malnutrition, and the need for surgery, thereby improving long-term outcomes.
Induction Vs Maintenance Therapy
Induction Therapy Goal:
The primary goal of induction therapy is to rapidly and effectively achieve clinical remission and mucosal healing in newly diagnosed patients or during a disease flare-up.
Maintenance Therapy Goal:
Maintenance therapy aims to sustain remission, prevent relapses, minimize long-term complications, and improve quality of life after induction therapy has successfully achieved remission.
Key Differences:
Induction therapies often utilize more potent agents (e.g., corticosteroids, biologics) at higher doses to achieve rapid control, whereas maintenance therapies focus on less intensive, long-term strategies to prevent recurrence, balancing efficacy with safety and tolerability.
Pediatric Considerations:
In pediatric IBD, treatment selection considers not only disease activity and location but also growth, development, psychosocial impact, and long-term safety profiles to minimize effects on pubertal development and overall well-being.
Induction Therapies
Corticosteroids:
First-line for moderate-to-severe active disease
For UC: Budesonide (localized ileal/colonic release) or systemic corticosteroids (prednisolone, methylprednisolone)
For CD: Systemic corticosteroids
Doses vary based on severity
Goal is rapid symptomatic relief
Tapering is crucial to minimize side effects.
Biologics:
Induction with anti-TNF agents (infliximab, adalimumab) or other biologics (e.g., vedolizumab, ustekinumab) for moderate-to-severe disease, especially when corticosteroids fail or are contraindicated
Typically given intravenously or subcutaneously at higher initial doses
Infliximab 5 mg/kg at weeks 0, 2, and 6 is a common induction regimen.
Immunomodulators:
Used as adjunctive therapy with biologics or as monotherapy for mild-to-moderate disease
Azathioprine, 6-mercaptopurine (6-MP), and methotrexate are common
Induction of effect can take weeks to months, so they are less suited for rapid control of severe flares alone.
Nutritional Therapy:
Exclusive enteral nutrition (EEN) is highly effective for inducing remission in pediatric CD and is comparable to corticosteroids, particularly in mild-to-moderate disease
It also supports nutritional status and growth
Can be used as a primary induction strategy or adjunctively.
Maintenance Therapies
Immunomodulators:
Long-term maintenance with azathioprine, 6-MP, or methotrexate is a cornerstone of therapy to maintain remission, particularly in patients treated with biologics, allowing for reduced biologic dosing and preventing antibody formation
Typical doses: Azathioprine 1-2.5 mg/kg/day
6-MP 1-1.5 mg/kg/day.
Biologics:
Continuous or intermittent administration of anti-TNF agents or other biologics at regular intervals (e.g., infliximab every 8 weeks, adalimumab every 2 weeks) to maintain remission in moderate-to-severe disease
Dosing adjustments may be needed based on drug levels and clinical response.
5-aminosalicylates (5-ASA):
Primarily used for mild-to-moderate ulcerative colitis, particularly distal disease or proctitis
Mesalamine formulations (oral and rectal) are used for maintenance of remission
Less effective for Crohn's disease
Doses vary widely based on formulation.
Dietary Management:
While not primary maintenance therapy, dietary modifications and nutritional support may be important to ensure adequate growth and manage symptoms in some children
Avoidance of triggers may be beneficial for individual patients.
Drug Specifics And Monitoring
Steroid Side Effects:
Long-term steroid use can cause growth deceleration, Cushingoid features, osteoporosis, cataracts, and increased infection risk
Careful monitoring and timely tapering are essential.
Biologic Monitoring:
Monitoring for infusion reactions, infections (including opportunistic infections like tuberculosis), development of antibodies to biologics, and laboratory abnormalities (e.g., liver function tests, complete blood count)
Therapeutic drug monitoring (TDM) helps optimize dosing.
Thioguanine Nucleotide Levels:
For azathioprine/6-MP, monitoring thioguanine nucleotide (TGN) levels can help assess therapeutic efficacy and personalize dosing to minimize toxicity and maximize benefit.
Genetic Testing:
Consider testing for TPMT (thiopurine S-methyltransferase) and NUDT15 gene variants prior to starting thiopurines to predict risk of severe myelosuppression.
Complications And Prognosis
Growth Failure:
A significant complication in pediatric IBD, often multifactorial
Prompt treatment to achieve remission and adequate nutritional support are key to recovery.
Extraintestinal Manifestations:
Arthritis, skin lesions (erythema nodosum, pyoderma gangrenosum), eye inflammation (uveitis, episcleritis), and liver disease (autoimmune hepatitis, primary sclerosing cholangitis) can occur and require specific management.
Surgical Indications:
Surgery may be required for refractory disease, complications like strictures, fistulas, toxic megacolon, or malignancy
Early intervention can improve outcomes.
Prognosis:
With modern therapies, the prognosis for pediatric IBD has significantly improved
Early diagnosis and aggressive management of induction and maintenance are crucial for achieving long-term remission, normal growth, and good quality of life.
Key Points
Exam Focus:
Differentiate induction vs
maintenance goals and agent choices
Understand specific pediatric considerations like growth and EEN
Recall key biologics and immunomodulators used in IBD.
Clinical Pearls:
Always taper corticosteroids slowly
Consider EEN as a potent induction agent for pediatric CD
Monitor thiopurine metabolites and TPMT/NUDT15 status
Early aggressive treatment improves long-term outcomes.
Common Mistakes:
Prolonged steroid use without adequate tapering
Underestimating the role of nutrition in pediatric IBD
Delaying biologic therapy in moderate-to-severe disease
Inadequate monitoring of immunosuppressive agents.