What is the diagnostic workup and treatment approach for a patient presenting with symptoms suggestive of Crohn's disease?

Crohn's Disease: Clinical Presentation and Diagnostic Workup

Clinical Presentation

Crohn's disease typically presents with chronic diarrhea (>6 weeks), abdominal pain, weight loss, and systemic symptoms including fever and malaise, often accompanied by elevated inflammatory markers. 1

Core Gastrointestinal Symptoms

• Diarrhea lasting more than 6 weeks is the hallmark symptom, with severe flares producing at least 10 loose stools daily 1, 2
• Abdominal pain occurs daily during moderate to severe flares, typically colicky in nature reflecting active intestinal inflammation 2, 3
• Weight loss develops from both malabsorption and reduced oral intake, serving as a key indicator of disease severity 2, 3

Systemic Manifestations

• Fever is more common in Crohn's disease than ulcerative colitis and helps distinguish between the two conditions 2
• Malaise and anorexia are systemic features that differentiate Crohn's exacerbations from other inflammatory bowel conditions 2

Extraintestinal Manifestations

• Osteoporosis, inflammatory arthropathies, scleritis, nephrolithiasis, cholelithiasis, and erythema nodosum may be present 3
• Primary sclerosing cholangitis, avascular necrosis, and sacroiliitis can also occur 1

Disease Distribution

• 25% of patients have colitis only, 25% have ileitis only, and 50% have ileocolitis 4
• The disease can affect any part of the gastrointestinal tract from mouth to anus, though terminal ileum and proximal colon are most frequently involved 4, 5

Initial Laboratory Workup

Begin with inflammatory markers (CRP, ESR), fecal calprotectin, complete blood count, and albumin to assess for inflammation and nutritional status. 1

Essential Laboratory Tests

• C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) to detect inflammation, though CRP has lower sensitivity and may be normal even during flares 1, 6
• Fecal calprotectin is a reliable indicator of intestinal inflammation; levels >100 mg/g predict positive findings (43%), with >200 mg/g providing even higher diagnostic yield (65%) 1
• Complete blood count to assess for anemia, which suggests organic disease 3
• Serum albumin to evaluate both inflammation and nutritional status 1
• Vitamin B12, folate, and vitamin D levels to assess nutritional status 3

Important Caveat

• Patients with chronic abdominal pain or diarrhea as their only symptoms, without evidence of biomarkers associated with Crohn's disease, should not undergo capsule endoscopy, as diagnostic yield is significantly lower (0% in some studies) 1

Diagnostic Algorithm

Ileocolonoscopy with segmental biopsies is the first-line investigation, followed by small bowel imaging with MR enterography or CT enterography to assess disease extent and complications. 1

Step 1: Ileocolonoscopy with Biopsies

• Ileocolonoscopy with segmental colonic and ileal biopsies should be performed when Crohn's disease is suspected and the procedure is clinically safe 1
• Biopsies should be obtained even from normal-appearing mucosa to look for microscopic disease 1
• Non-caseating granulomas are generally accepted as histological proof of Crohn's disease, though their absence does not exclude the diagnosis 7, 5
• Ileoscopy with biopsy histology is superior in establishing the diagnosis of mild ileal Crohn's disease 1

Step 2: Cross-Sectional Imaging

• MR enterography (MRE) is preferred as first-line imaging because it does not expose patients to ionizing radiation and has similar diagnostic accuracy to CT enterography 1
• CT enterography (CTE) is appropriate when MRE is unavailable or in emergency settings, with short acquisition time (<2 seconds) 1
• Both require oral contrast material ingestion (900-1,500 mL over 45-60 minutes) to achieve adequate bowel distention 1
• Coverage should include the perineum to facilitate detection of perianal Crohn's disease, even without specific concern for perianal fistula 1
• Intestinal ultrasound (IUS) may be used as an alternative where local expertise exists, though MRE has greater sensitivity for small bowel disease extent (80% vs 70%) and specificity (95% vs 81%) 1

Step 3: Capsule Endoscopy (When Indicated)

Capsule endoscopy should be performed when clinical features are consistent with Crohn's disease but ileocolonoscopy and imaging studies are negative or inconclusive. 1

• Capsule endoscopy has equivalent or higher diagnostic yield than ileoscopy, radiography, and CT enterography, but not MR enterography 1
• The Lewis score ≥135 on capsule endoscopy predicts confirmed Crohn's disease diagnosis in 82.6% of patients during follow-up, compared to only 12.1% with scores <135 1
• A patency capsule should be used prior to capsule endoscopy in patients with suspected Crohn's disease who have obstructive symptoms, history of small bowel resection, or known stenosis 1
• The risk of capsule retention in patients with suspected Crohn's disease without obstructive symptoms is low and comparable to obscure GI bleeding 1

Important Limitations

• Capsule endoscopy alone cannot diagnose Crohn's disease, as it reports inflammatory activity independently of etiology 1
• Minor mucosal abnormalities found during capsule endoscopy can be seen in normal individuals, particularly those using NSAIDs, and may be insufficient in isolation to diagnose Crohn's disease 6

Upper Gastrointestinal Evaluation

Upper gastrointestinal endoscopy is not routinely required unless patients have upper gastrointestinal symptoms. 1

• Upper GI involvement occurs in 0.5-13% of patients with ileocolonic Crohn's disease, though early signs may be detected radiologically in 20-40% 7
• Patients with upper GI Crohn's disease more frequently have colic-like abdominal pain, nausea, anorexia, and are younger at disease onset 7

Disease Activity Assessment

Use standardized scoring systems to objectively measure disease activity, as symptoms and inflammation can be disconnected. 2, 6

Clinical Scoring Systems

• Crohn's Disease Activity Index (CDAI): moderate disease defined as CDAI 220-450, severe disease as CDAI >450 2, 4
• Harvey-Bradshaw Index (HBI): simpler clinical assessment using general well-being, abdominal pain, liquid stool frequency, abdominal mass, and extraintestinal manifestations 2, 4

Objective Monitoring

• Inflammation often persists in the absence of gastrointestinal symptoms and may lead to progressive bowel damage and complications such as fistulae, abscesses, and strictures 6
• Patients with unexpectedly raised CRP but no localizing symptoms should have fecal calprotectin measured to validate biochemical disease activity before arranging endoscopic evaluation 6

Special Diagnostic Scenarios

Inflammatory Bowel Disease Type Unclassified (IBDU)

• In up to 10% of patients with IBD affecting the colon, it may be impossible to distinguish between Crohn's disease and ulcerative colitis after ileocolonoscopy and small-bowel imaging 1
• Capsule endoscopy has demonstrated small bowel lesions compatible with Crohn's disease in 17-70% of patients with IBDU, though a negative capsule endoscopy cannot definitively exclude future Crohn's disease diagnosis 1

Postoperative Recurrence

• In patients with suspected small-bowel recurrence after colectomy undiagnosed by ileocolonoscopy or imaging studies, capsule endoscopy is strongly recommended 1
• Endoscopic recurrence at the neoterminal ileum occurs in 30-90% of patients within 12 months of surgery and almost universally by 5 years 4

Common Pitfalls to Avoid

• Do not rely solely on symptom assessment, as inflammation can be present without causing noticeable symptoms, leading to underdiagnosis or delayed diagnosis 6
• Do not perform capsule endoscopy in patients with chronic pain/diarrhea alone without positive inflammatory markers, as diagnostic yield is extremely low (0% in patients with both symptoms but negative markers) 1
• Do not skip patency capsule assessment in patients with established Crohn's disease, obstructive symptoms, or known stenosis before performing capsule endoscopy 1
• Do not attribute minor endoscopic or radiologic findings to Crohn's disease in asymptomatic patients, particularly if they have recently used NSAIDs 6