What is the best course of treatment for a patient with Crohn's disease and a normal computed tomography (CT) scan?

Crohn's Disease with Normal CT: Clinical Approach

A normal CT scan does not exclude active Crohn's disease, and treatment decisions should be guided by the complete clinical picture including symptoms, endoscopic findings, and biomarkers rather than CT results alone. 1, 2

Understanding Why CT Can Be Normal Despite Active Disease

Critical limitation: CT enterography has a sensitivity of only 75-90% for detecting Crohn's inflammation, meaning it misses 10-25% of cases even under optimal conditions 2. Standard CT abdomen/pelvis with IV contrast has even lower sensitivity 2.

The imaging can appear normal in several scenarios:

• Proximal small bowel disease - CT has higher sensitivity for terminal ileal disease compared to more proximal jejunal involvement 2
• Early or mild mucosal inflammation - Subtle inflammatory changes may not produce classic CT findings like wall thickening, mural stratification, or comb sign 2
• Inadequate bowel distention - Without proper enterography technique, collapsed bowel loops obscure inflammatory changes 2
• Enteroenteric fistulas - These have particularly poor detection rates, with only 20% sensitivity on standard CT 2

Diagnostic Algorithm When CT Is Normal

Step 1: Verify the CT Protocol Used

• Was it CT enterography? This requires neutral oral contrast (>900 mL over 45-60 minutes) plus IV contrast for optimal sensitivity 1
• Standard CT with IV contrast? Has lower sensitivity but still useful 2
• Non-contrast CT? Has markedly poorer performance and cannot adequately assess active inflammation - should not be relied upon 2

Step 2: Pursue Endoscopic Evaluation

Colonoscopy with ileoscopy remains the reference standard and can detect mucosal inflammation not visible on CT 1. This is essential because:

• In one cohort of 150 Crohn's patients, 36 had active small bowel disease on CT enterography following a normal ileocolonoscopy 1
• Conversely, CT can show extensive inflammation when ileoscopy appears normal 1
• Ileoscopy with biopsy is superior for establishing diagnosis of mild ileal Crohn's disease 1

Step 3: Consider MR Enterography

• MRE should be used rather than repeat CTE when possible, especially for younger patients (<35 years old) to avoid radiation exposure 1
• MRE has similar diagnostic accuracy to CTE and may detect inflammation missed on prior CT 1
• MRE is preferred for monitoring treatment response in non-acute patients due to its multiparametric nature 1

Step 4: Utilize Biomarkers for Disease Activity

Objective markers of inflammation are essential surrogates for endoscopy:

• Fecal calprotectin - Treatment escalation/de-escalation driven by calprotectin plus clinical variables results in improved endoscopic and quality of life outcomes 1
• CRP levels - Helps assess systemic inflammation 1
• These biomarkers should guide therapy changes even when imaging appears normal 1

Treatment Approach Based on Disease Severity

For Mild Disease (Low-Risk Patients)

Budesonide is recommended for induction of remission in ambulatory outpatients with low-risk, mild ileal or ileocolonic Crohn's disease 3.

For colonic disease:

• Sulfasalazine is a reasonable choice 3
• Other aminosalicylates have no role in CD treatment 3

Maintenance therapy options for select mild-moderate patients:

• Azathioprine 3
• Vedolizumab (gut-specific biologic) 3

For Moderate-to-Severe Disease

First-line therapy consists of corticosteroids for rapid symptom palliation during initiation of anti-TNF therapy 4.

Anti-TNF agents are highly effective for inducing remission:

• Adalimumab dosing for adults: 160 mg on Day 1,80 mg on Day 15, then 40 mg every other week starting Day 29 5
• Aminosalicylates and/or corticosteroids may be continued during anti-TNF treatment 5
• Azathioprine, 6-mercaptopurine, or methotrexate may be continued if necessary 5

For pediatric patients ≥6 years with moderate-to-severe CD:

• Weight-based dosing: 17-40 kg receive 80 mg Day 1,40 mg Day 15, then 20 mg every other week 5
• ≥40 kg receive adult dosing 5

Exclusive Enteral Nutrition

Recommended as first-line treatment for inducing remission in pediatric CD 6. Recent evidence suggests long-term enteral supplementation (approximately half of daily calories) may maintain remission 6.

Monitoring Strategy

Adopt a "treat-to-target" approach with tight control:

• Target full remission (both clinical and endoscopic) rather than just symptom response 7
• Use combination of surrogate measures (fecal calprotectin), endoscopy, and cross-sectional imaging at intervals 1
• Choice of monitoring modality depends on disease distribution, severity, and patient preference 1

Endoscopic monitoring:

• Simple Endoscopic Score for Crohn's Disease (SES-CD) is the gold standard for measuring disease activity 1
• Mucosal biopsy specimens are essential for complete assessment 1

Critical Pitfalls to Avoid

• Never rule out active Crohn's disease based solely on negative standard CT without enterography protocol 2
• Do not assume normal CT excludes complications - fistulas (especially enteroenteric) have variable detection rates of 20-100% sensitivity 2
• Do not use non-contrast CT for evaluating suspected flares - it has poorer performance and cannot adequately assess active inflammation 2
• Do not rely on corticosteroids or 5-aminosalicylates for maintenance therapy - evidence does not support their use 6
• Up to 20% of patients have isolated proximal small bowel disease beyond the reach of complete ileocolonoscopy - imaging is complementary to endoscopy 1

When to Consider Surgery

Surgical intervention is required in up to two-thirds of CD patients during their lifetime 8. Indications include:

• Medically refractory disease 8
• Perforation 8
• Persisting or recurrent obstruction 8
• Abscess not amenable to percutaneous drainage 8
• Intractable hemorrhage 8
• Dysplasia or cancer 8