What is the best course of action for a 25-month-old male with significant growth faltering, history of anemia, elevated calprotectin, and a substantial drop in weight and height percentiles, despite a standard GI (Gastrointestinal) workup being unrevealing?

Evaluation and Management of Growth Faltering with Elevated Calprotectin

This child requires upper and lower endoscopy with biopsies to evaluate for inflammatory bowel disease (IBD), specifically Crohn's disease, given the severe growth faltering (60 percentile point weight drop, 40 percentile point height drop), mildly elevated calprotectin (56 μg/g), and history of iron deficiency anemia requiring prolonged treatment.

Rationale for Endoscopic Evaluation

Growth Faltering as a Red Flag for IBD

• Upper GI endoscopy is mandatory in pediatric patients with suspected IBD where growth failure is present, as it helps differentiate between ulcerative colitis and Crohn's disease and confirms the diagnosis 1
• Growth retardation occurs in up to 40% of children and adolescents with Crohn's disease, with nearly 90% showing decreased height and/or growth velocity below the 3rd percentile even before diagnosis is made 1
• Marked growth retardation is considered a factor predictive of poor outcome and requires aggressive diagnostic evaluation 1
• The severity of this child's growth faltering (dropping 60 percentile points for weight and 40 for height) represents significant pathology that warrants invasive investigation 1

Calprotectin Interpretation

• While a calprotectin of 56 μg/g is only mildly elevated (normal <50 μg/g), calprotectin has 84% sensitivity and 74% specificity for detecting endoscopic disease activity 1
• In the context of severe growth faltering and anemia, even mildly elevated calprotectin supports the need for endoscopic evaluation rather than dismissing IBD 1
• The "unrevealing" standard GI workup likely did not include endoscopy, which is the definitive diagnostic test 1

Anemia as a Supporting Feature

• The history of anemia requiring 5 months of daily oral iron suggests chronic iron deficiency, which is common in Crohn's disease due to chronic inflammation and malabsorption 1
• Iron deficiency anemia in the context of growth faltering warrants bidirectional endoscopy to evaluate for mucosal disease 1

Recommended Diagnostic Approach

Immediate Next Steps

• Perform bidirectional endoscopy (upper GI endoscopy and colonoscopy with ileoscopy) with multiple biopsies 1
• Obtain at least two biopsies from five sites around the colon including the rectum and terminal ileum 1
• Take biopsies from both inflamed and normal-appearing mucosa, as histological activity may be present even in endoscopically normal areas 1
• Upper GI biopsies are essential in pediatric IBD evaluation as upper GI tract inflammation can occur without localizing symptoms 1

Additional Pre-Endoscopy Testing

• Test for celiac disease with tissue transglutaminase IgA and total IgA, as celiac disease can present with growth faltering and anemia 1
• Check inflammatory markers (CRP, ESR) to assess for systemic inflammation 1
• Obtain complete nutritional assessment including albumin, prealbumin, vitamin D, vitamin B12, and folate levels 1

Critical Timing Considerations

• Growth failure in Crohn's disease is best described in terms of growth velocity over 6-12 months, and this child has already lost substantial growth potential 1
• Early diagnosis and treatment are essential, as failure to recognize and treat growth faltering in the first two years of life may result in decreased adult height and cognitive potential 2
• At 25 months of age, this child is approaching the critical window where catch-up growth becomes increasingly difficult 1

Common Pitfalls to Avoid

• Do not rely on a "normal" standard GI workup to exclude IBD - endoscopy with biopsies is the gold standard 1
• Do not dismiss mildly elevated calprotectin in the context of severe growth faltering and anemia 1
• Avoid delaying endoscopy for empiric nutritional trials when red flags for organic disease are present 1
• Do not assume growth faltering is purely nutritional when there is objective evidence of inflammation (elevated calprotectin) and chronic anemia 1

If IBD is Confirmed

• Initiate appropriate medical therapy promptly, as corticosteroids should be avoided as much as possible due to negative effects on growth 1
• Consider exclusive enteral nutrition (EEN) as first-line therapy in pediatric Crohn's disease, which can induce remission while supporting growth 1
• Monitor growth velocity closely using Z-scores every 3-6 months 1
• Evaluate bone age to assess remaining potential for catch-up growth 1