What is the recommended diagnostic work‑up and step‑wise treatment strategy for an adult with suspected inflammatory bowel disease, including management of ulcerative colitis and Crohn disease?

Diagnostic Work-Up and Treatment Strategy for Inflammatory Bowel Disease

Ileocolonoscopy with terminal ileal intubation and segmental biopsies is the essential first-line investigation for suspected IBD, complemented by cross-sectional imaging (preferably MR enterography) to assess small bowel disease extent and exclude complications. 1, 2

Initial Diagnostic Approach

Mandatory First-Line Investigations

Ileocolonoscopy with biopsies is the cornerstone diagnostic test that must be performed in all patients with suspected IBD 1, 2. This procedure allows:

• Direct visualization of mucosal inflammation patterns 2
• Terminal ileal assessment (critical since 36% of Crohn's disease patients have isolated ileal disease) 1, 2
• Collection of segmental biopsies from at least five sites including ileum and rectum (minimum two biopsies per site) 1, 2
• Documentation of skip lesions and microscopic inflammation 2

Before endoscopy, obtain stool studies to exclude infectious mimics 1, 3, 2:

• Bacterial culture
• Clostridium difficile toxin assay
• Ova and parasites 2

Fecal calprotectin testing helps stratify patients 3, 2:

• <50 μg/g effectively rules out active IBD (93-95% sensitivity) 3, 2

• 100-250 μg/g warrants ileocolonoscopy 3

• Cannot replace endoscopy but useful for triage 2

Cross-Sectional Imaging

MR enterography (MRE) is preferred as first-line imaging over CT enterography to avoid radiation exposure, particularly in young patients 1. MRE is essential because:

• Up to 20% of Crohn's disease patients have isolated proximal small bowel disease beyond endoscopic reach 1
• MRE demonstrates 80% sensitivity for small bowel disease extent versus 70% for intestinal ultrasound 1
• Detects extraluminal complications (strictures, fistulae, abscesses) 1

Intestinal ultrasound (IUS) is an acceptable alternative depending on local expertise, with similar value to MRE for monitoring transmural healing 1.

CT enterography should be reserved for acute presentations only, given radiation exposure risks (15.5% of patients accumulate >75 mSv lifetime dose) 1.

Additional Baseline Testing

Obtain comprehensive laboratory evaluation 2:

• Complete blood count
• CRP (though 20% of active Crohn's disease patients have normal CRP) 2
• Albumin
• Liver function tests
• Vitamin B12 and iron studies
• Kidney function 2

Upper Endoscopy Indications

Esophagogastroduodenoscopy is NOT routinely required unless patients have upper gastrointestinal symptoms 1. This represents a key change from older practice patterns.

Distinguishing Ulcerative Colitis from Crohn's Disease

Ulcerative Colitis Features

Endoscopic characteristics 1, 4:

• Continuous inflammation starting distally in rectum with proximal extension 1, 4

• 97% have rectal involvement 4

• Loss of vascular pattern, mucosal granularity, and friability 4
• Superficial ulcerations 4

Histological features 1, 4:

• Basal plasmacytosis
• Diffuse crypt atrophy and distortion
• Crypt abscesses
• Absence of granulomas 1, 4

Important caveats 1, 4:

• Rectal sparing occurs in up to 3% of UC patients 4
• "Backwash ileitis" (mild terminal ileal inflammation) occurs in up to 20% with pancolitis 1, 4
• Cecal patch and peri-appendiceal inflammation can occur in UC 1

Crohn's Disease Features

Endoscopic characteristics 4:

• Skip lesions with segmental, asymmetric distribution 4
• Aphthous ulcers progressing to longitudinal ulcers 4
• Cobblestone appearance 4
• Perianal lesions and strictures 4
• Can occur anywhere in GI tract 4

Histological features 4:

• Non-caseating granulomas (pathognomonic when present) 4
• Transmural inflammation 4
• Focal, asymmetric inflammation 4

In 5-15% of cases, endoscopic and histological assessment cannot definitively distinguish between Crohn's colitis and UC 1.

Stepwise Treatment Strategy

Ulcerative Colitis Management

For mild-to-moderate disease 1:

• 5-aminosalicylic acid (5-ASA) remains first-line therapy
• Topical therapy for distal disease
• Oral therapy for extensive disease

For moderate-to-severe disease 1:

• Corticosteroids for acute flares
• Immunomodulators (thiopurines, methotrexate) for steroid-dependent disease
• Advanced therapies (anti-TNF, JAK inhibitors) for steroid-refractory disease

For acute severe ulcerative colitis (ASUC) 1:

• Intravenous corticosteroids
• Oral JAK inhibitors may be considered in corticosteroid-refractory cases via multidisciplinary team approach 1

Maintenance strategy 1:

• Patients achieving prolonged remission with immunomodulators/advanced therapies can discontinue 5-ASA 1
• Withdrawal of purine analogues or anti-TNF therapy carries significant relapse risk requiring shared decision-making 1

Crohn's Disease Management

Treatment targets have evolved 1:

• Clinical symptom control alone is insufficient
• Objective measures (endoscopic healing, cross-sectional imaging, fecal calprotectin) should guide therapy 1
• Multimodal monitoring approach recommended 1

Therapeutic approach 1:

• Immunomodulators (thiopurines, methotrexate) for maintenance
• Anti-TNF therapy for moderate-to-severe disease
• Combination therapy often superior to monotherapy
• Withdrawal of therapy carries significant relapse risk 1

Perianal Crohn's disease requires specialized management 1:

• Pelvic MRI and examination under anesthesia by experienced colorectal surgeon 1
• Endoscopic assessment of rectal mucosa 1
• Seton placement to prevent sepsis 1
• Multidisciplinary team management essential 1

Monitoring Strategy

Multimodal approach for both UC and Crohn's disease 1:

• Clinical assessment
• Biochemical markers (CRP, fecal calprotectin) 1
• Endoscopic evaluation with histology 1
• Cross-sectional imaging for Crohn's disease 1

Fecal calprotectin monitoring 1, 3:

• Serial measurements at 3-6 month intervals facilitate early recognition of flares 3
• Thresholds of 200-250 μg/g predict endoscopic remission 3

Histological remission may be used as adjunct to endoscopic remission but is not mandatory treatment target 1.

Critical Pitfalls to Avoid

Do not perform sigmoidoscopy alone when full ileocolonoscopy is feasible, as this misses right-sided colonic and ileal disease in Crohn's disease 2.

Do not rely on CRP alone to exclude active disease, as 20% of Crohn's patients with active inflammation have normal CRP 2.

Do not assume normal stool frequency equals remission, as 27% of patients with complete endoscopic and histologic healing continue having increased stool frequency 3.

Do not skip infectious workup even in known IBD patients, as superimposed infection alters management 3, 2.

Do not use CT enterography routinely for monitoring given cumulative radiation exposure; reserve for acute presentations 1.