What is the diagnostic approach and management for an infant presenting with symptoms suggestive of Inflammatory Bowel Disease (IBD), such as persistent diarrhea, abdominal pain, and failure to thrive?

Presentation of IBD in Infants

Clinical Presentation and Key Features

Infants with IBD present with distinct clinical patterns that differ significantly from older children and adults, most notably with persistent bloody diarrhea, failure to thrive, and more extensive colonic involvement rather than ileocolonic disease. 1, 2, 3

Cardinal Symptoms to Recognize

• Persistent bloody diarrhea that extends beyond the typical viral gastroenteritis course (>2 weeks) is the hallmark presentation 2, 4
• Failure to thrive and growth failure manifesting as poor weight gain, which occurs in approximately 14% of very-early-onset Crohn's disease (VEO-CD) cases 3, 4
• Abdominal pain is paradoxically less common in infants with VEO-IBD compared to older children (p=0.000 for VEO-CD) 3
• Fever and diarrhea are significantly more common in VEO-CD (p=0.008 and p=0.001 respectively) 3
• Perianal disease when present, should prompt immediate endoscopic evaluation 5

Disease Distribution Patterns

• Infants under 6 years demonstrate more extensive colitis and less ileitis compared to older children and adults 1, 2, 3
• Colonic phenotype predominates in VEO-IBD (p=0.002), while ileocolonic disease is more characteristic of late-onset IBD 3
• Upper gastrointestinal involvement occurs more frequently in pediatric IBD, affecting up to 30% of children with macroscopic disease 6

Diagnostic Approach

Initial Laboratory Screening

Before initiating any immunosuppression, obtain comprehensive laboratory screening including complete blood count, inflammatory markers, infectious workup, and immunodeficiency evaluation. 1

• Fecal calprotectin ≥250 μg/g is highly sensitive for IBD (AUC 0.967) and should be measured in all suspected cases 5

  • Critical caveat: Calprotectin is present in human breast milk, making interpretation difficult in breastfed infants 6
  • Lactoferrin similarly cannot be reliably interpreted in breastfed infants 6

• C-reactive protein >10 mg/L combined with symptoms and fecal calprotectin achieves optimal diagnostic accuracy (AUC 0.997) 5

• Hemoglobin <-2 SD for age and sex helps stratify risk 5

• Stool cultures and infectious workup are mandatory to exclude bacterial gastroenteritis, parasitic infections (especially Giardia), and other infectious etiologies before diagnosing IBD 6, 1

Immunodeficiency Screening for Infants

Children presenting under age 5-6 years require mandatory evaluation for underlying primary immunodeficiency disorders before initiating standard IBD therapy, as VEO-IBD may represent monogenic disorders. 1, 2, 7

• Obtain IgG, IgA, and IgM levels to screen for common variable immunodeficiency (CVID), which presents with IgG <5 g/L plus low IgA or IgM 6
• Consider genomic testing for VEO-IBD patients to identify monogenic disorders affecting neutrophils, T-cells, B-cells, macrophages, or enterocyte function 1, 2, 7
• Screen for immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome and other immune defects 7

Endoscopic Evaluation

Ileocolonoscopy with biopsies from multiple sites is essential for all infants with suspected IBD, and upper endoscopy (EGD) is mandatory to improve diagnostic accuracy. 1, 2

• Obtain multiple biopsies from the ileum and each colonic segment, including rectum, from both abnormal and normal-appearing areas 1, 2
• Upper endoscopy is not optional in pediatric IBD evaluation—it improves diagnostic accuracy and helps differentiate Crohn's disease from ulcerative colitis 1, 2
• Look for granulomas, which occur with higher frequency in pediatric patients and aid diagnosis 1

Additional Screening Requirements

• Hepatitis B and C serologies, varicella zoster virus serology, Epstein-Barr virus serology before immunosuppression 1
• Tuberculosis screening with interferon-gamma release assay 6, 1
• Colonoscopy should be performed with low threshold in infants with diarrhea, growth failure, or anemia to detect IBD 6

Management Strategy

Treatment Algorithm Based on Disease Severity

For mild to moderate Crohn's disease in infants, exclusive enteral nutrition (EEN) is first-line induction therapy, providing a critical window to update vaccination status before immunosuppression. 1

• EEN at diagnosis allows time to complete routine childhood vaccinations, inactivated vaccines, and update immunization status 1
• For infants whose mothers received biologics during pregnancy, withhold live vaccines until at least 6 months of age 1

For severe disease at presentation or poor prognostic factors, initiate biologic TNF antagonist therapy early rather than step-up approach. 1

• Severe persistent symptoms despite initial therapy warrant early biologic initiation 1
• Avoid 5-aminosalicylates for induction or maintenance in moderate pediatric Crohn's disease 6, 1

Nutritional Management

Increase energy and protein intake to 150% of recommended daily allowances for height and age, as malnutrition is primarily responsible for growth failure. 4

• Consider nocturnal nasogastric infusion as supplement to daily intake 4
• Nutritional support is as effective as steroids for achieving remission in children 4
• No significant difference between elemental versus polymeric diets 4

Monitoring and Treatment Targets

Assess for mucosal healing within 1 year of treatment initiation using objective markers like fecal calprotectin in patients achieving clinical remission. 1

• Monitor growth parameters (height, weight, pubertal development) at every visit, as growth failure indicates undertreatment 1, 4
• Growth retardation during medical treatment equals undertreatment in pediatrics 4
• Monitor bone health including vitamin D and calcium levels, consider bone density assessment with chronic disease or prolonged steroid exposure 1

Critical Pitfalls to Avoid

• Do not dismiss persistent diarrhea as viral gastroenteritis in infants—bloody diarrhea beyond typical viral course warrants IBD evaluation 2, 4
• Do not delay immunodeficiency screening in children under 6 years—these patients may require targeted therapy for specific genetic defects rather than standard immunosuppression 1, 7
• Do not rely on lactoferrin or fecal leukocytes in breastfed infants—these markers are unreliable due to presence in human milk 6
• Do not skip upper endoscopy—it is mandatory in pediatric IBD evaluation, not optional 1, 2
• Do not accept growth failure as acceptable disease control—it indicates inadequate treatment requiring intensification 4
• Do not misdiagnose as depression or psychiatric disorder—some children present with abdominal pain and depression as initial IBD manifestations 4