What is the appropriate diagnostic workup and stepwise medical management for an adult with newly diagnosed Crohn's disease presenting with abdominal pain, bloody diarrhea, weight loss, and fatigue?

Diagnostic Workup and Stepwise Medical Management for Newly Diagnosed Crohn's Disease

For an adult presenting with abdominal pain, bloody diarrhea, weight loss, and fatigue, perform ileocolonoscopy with segmental biopsies plus cross-sectional small bowel imaging (MR enterography preferred), then initiate treatment based on disease severity: mild ileocolonic disease with high-dose mesalazine 4 g daily or budesonide 9 mg daily for isolated ileocecal involvement; moderate-to-severe disease with prednisolone 40 mg daily tapered over 8 weeks; and severe disease with intravenous corticosteroids plus consideration for early biologic therapy. 1

Initial Diagnostic Evaluation

Essential History Elements

• Stool characteristics: frequency (mild disease: few stools daily; severe flares: ≥10 loose stools daily), consistency, presence of blood, urgency 2, 3
• Abdominal pain pattern: daily colicky pain indicates active inflammation; persistent pain without inflammatory markers may reflect visceral hypersensitivity or strictures 2, 3
• Constitutional symptoms: fever (more common in Crohn's than ulcerative colitis), malaise, anorexia, weight loss magnitude 1, 4, 3
• Perianal symptoms: fistulae, abscesses (may be initial presentation) 3, 5
• Extraintestinal manifestations: joint pain/arthritis (present in up to 40% of patients), eye symptoms, skin lesions 3, 1
• Risk factors: smoking status, recent travel, medication use (NSAIDs), family history 1

Physical Examination Priorities

• Vital signs including temperature (fever suggests active Crohn's vs. ulcerative colitis) 1, 4
• Weight and nutritional status assessment 1
• Abdominal examination for tenderness, masses (right iliac fossa mass suggests ileocecal disease), distension 1
• Mandatory perianal examination for fistulae, abscesses, skin tags 1, 5
• Signs of anemia, dehydration 1, 3

Laboratory Investigations

Initial blood work 1:

• Complete blood count (anemia from chronic inflammation/bleeding) 3
• Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) - elevated CRP reflects inflammatory burden 2, 3
• Serum albumin (low indicates inflammation and malnutrition) 2
• Electrolytes, liver function tests 1

Stool studies 1:

• Fecal calprotectin (noninvasive marker of intestinal inflammation with high sensitivity/specificity for distinguishing IBD from IBS) 2, 4
• Microbiological testing including Clostridium difficile toxin 1
• Consider cytomegalovirus testing in moderate-to-severe colitis, particularly if steroid-refractory 4

Abdominal radiography: essential to exclude colonic dilatation, assess for small bowel obstruction, or identify right iliac fossa mass 1

Endoscopic and Imaging Workup

First-Line Endoscopy

Ileocolonoscopy with biopsies is the primary diagnostic tool 1, 4:

• Intubate terminal ileum with segmental biopsies from ileum and all colonic segments (essential for detecting microscopic disease even when mucosa appears normal) 1
• Look for focal, asymmetric inflammation, aphthous ulcers, skip lesions, cobblestoning 1, 6
• Document extent using Simple Endoscopic Score for Crohn's Disease (SES-CD) 1
• Histology demonstrates focal, asymmetric, transmural, or granulomatous features 1, 6

Upper endoscopy: only perform if upper gastrointestinal symptoms present (not routine) 1

Cross-Sectional Small Bowel Imaging

Mandatory imaging to assess small bowel disease extent (20% of patients have isolated proximal small bowel disease beyond colonoscopy reach) 1:

• MR enterography (MRE): preferred first-line modality to avoid radiation exposure 1

  • Sensitivity 80% and specificity 95% for small bowel disease extent 1
  • Detects mural features (wall thickening, hyperenhancement, edema) and perienteric changes (engorged vasa recta, fibrofatty proliferation, lymphadenopathy) 1
  • Identifies penetrating complications (fistulae, abscesses, inflammatory masses) 1

• CT enterography: equivalent diagnostic accuracy to MRE but involves radiation exposure 1

• Small bowel ultrasound: reasonable alternative, particularly in younger patients, though slightly lower sensitivity (70%) than MRE 1

Key principle: Ileoscopy and radiological imaging are complementary—both are needed for complete assessment 1

Disease Severity Assessment

Clinical Activity Indices

• Crohn's Disease Activity Index (CDAI): moderate disease 220-450, severe disease >450 2, 6
• Harvey-Bradshaw Index (HBI): simpler assessment using general well-being, abdominal pain, liquid stool frequency, abdominal mass, extraintestinal manifestations 2

Disease Phenotype Classification (Montreal Classification) 6, 5

• Age at diagnosis: <16,17-40, >40 years
• Location: ileal (25%), colonic (25%), ileocolonic (50%)
• Behavior: inflammatory (nonstricturing/nonpenetrating), stricturing, or penetrating

Stepwise Medical Management

Mild Ileocolonic Disease

First-line therapy 1, 7:

• High-dose mesalazine 4 g daily for mild ileocolonic disease (Grade A evidence) 1
• Budesonide 9 mg daily for isolated ileocecal disease with moderate activity (marginally less effective than prednisolone but better side effect profile) 1, 7

Moderate-to-Severe Disease

Corticosteroid induction 1:

• Prednisolone 40 mg daily orally for moderate-to-severe disease or mild-to-moderate disease failing mesalazine (Grade A evidence) 1
• Taper gradually over 8 weeks according to severity and response (rapid reduction causes early relapse) 1

Severe Disease

Intravenous corticosteroids 1:

• Hydrocortisone 400 mg/day OR methylprednisolone 60 mg/day (Grade B evidence) 1
• Concomitant intravenous metronidazole often advisable (difficult to distinguish active disease from septic complications) 1
• Joint medical and surgical management with gastroenterologist and colorectal surgeon 1

Supportive measures for severe disease 1:

• Vital signs monitoring four times daily
• Intravenous fluid and electrolyte replacement
• Blood transfusion to maintain hemoglobin >10 g/dl
• Subcutaneous heparin for thromboembolism prophylaxis (Grade B)
• Nutritional support (enteral or parenteral) if malnourished (Grade C)

Maintenance Therapy Considerations

After induction of remission 1, 7:

• Select patients with mild-to-moderate disease may benefit from azathioprine/mercaptopurine or gut-specific biologics (vedolizumab) 7
• Close clinical monitoring with objective inflammatory markers (CRP, fecal calprotectin) to guide treatment escalation/de-escalation 1
• Target endoscopic remission (absence of ulcerations) predicts better long-term outcomes than symptomatic improvement alone 2

Common Pitfalls and Caveats

Diagnostic delays: Symptoms may mimic irritable bowel syndrome; weight loss, nocturnal diarrhea, fever, or systemic features should raise suspicion for underlying inflammatory disease 3

Incomplete evaluation: Up to 20% have isolated proximal small bowel disease—colonoscopy alone misses these cases; always perform cross-sectional imaging 1

Persistent pain without inflammation: May reflect visceral hypersensitivity, functional disorder, strictures, bile salt malabsorption, or bacterial overgrowth rather than active disease—requires evaluation beyond inflammatory markers 1, 3

Surgical considerations: At least 50% require surgery within 10 years; 70-80% within lifetime; surgery is not curative and postoperative medical therapy is mandatory 1, 4, 5

Psychosocial impact: Depression and anxiety are common comorbidities that negatively impact quality of life and disease outcomes—address proactively 3