What is the appropriate initial diagnostic workup and treatment strategy, including induction and maintenance therapy, for a newly diagnosed patient with Crohn's disease?

Initial Diagnostic Workup and Treatment Strategy for Newly Diagnosed Crohn's Disease

For newly diagnosed Crohn's disease, confirm diagnosis with ileocolonoscopy and biopsies combined with cross-sectional imaging (MR or CT enterography), then stratify treatment by disease severity: mild ileal/right colonic disease starts with budesonide 9 mg daily, while moderate-to-severe disease or high-risk features require immediate biologic therapy (anti-TNF agents) with or without immunomodulators to prevent disease progression and complications. 1, 2

Diagnostic Workup

Initial Clinical Assessment

• Obtain detailed history focusing on: chronic diarrhea (>4 weeks), abdominal pain location and character, rectal bleeding, weight loss, fever, perianal symptoms (pain, discharge, fistulas), and extraintestinal manifestations (arthritis, skin lesions, eye inflammation) 1, 3
• Physical examination must include: vital signs for hemodynamic stability, abdominal examination for masses or tenderness, perianal inspection for fissures/fistulas/abscesses, and assessment for extraintestinal manifestations 3

Laboratory Evaluation

• Initial blood work: complete blood count (anemia, leukocytosis), comprehensive metabolic panel (albumin, electrolytes), C-reactive protein, erythrocyte sedimentation rate 1, 3
• Fecal calprotectin is strongly recommended as it correlates with endoscopic inflammation (r=0.96) and has high negative predictive value to rule out inflammatory bowel disease 1, 3
• Consider serologic markers (ASCA, anti-OmpC) though these are adjunctive and not diagnostic 4

Endoscopic Evaluation

• Ileocolonoscopy with biopsies of the terminal ileum and all colonic segments is the gold standard for diagnosis, looking for: skip lesions, aphthous ulcers, cobblestoning, strictures, and obtaining biopsies showing focal, asymmetric, transmural inflammation or non-caseating granulomas 1, 5, 4
• Upper endoscopy should be considered if upper gastrointestinal symptoms are present 5
• The endoscopic findings must be documented using standardized scoring (CDEIS or SES-CD) to establish baseline disease activity 1

Cross-Sectional Imaging

• CT enterography or MR enterography is mandatory at diagnosis to assess small bowel involvement, disease extent, and exclude complications (strictures, fistulas, abscesses) that endoscopy cannot visualize 1, 5
• MR enterography is preferred in younger patients to avoid radiation exposure, with diagnostic accuracy equivalent to CT (sensitivity >80%, specificity >85%) 1
• CT enterography is faster and more readily available, particularly useful for first diagnosis and detecting complications 1
• Intestinal ultrasound by experienced operators can assess disease activity and monitor treatment response, though it has lower sensitivity for rectal disease 1

Risk Stratification

High-Risk Features Requiring Aggressive Therapy

• Age <40 years at diagnosis 6
• Extensive small bowel disease (>40 cm involvement) 1
• Deep ulcerations on endoscopy 1
• Perianal disease (fistulas, abscesses) 1, 6
• Stricturing or penetrating disease behavior 1, 6
• Requirement for corticosteroids at presentation 6
• Severe disease requiring hospitalization 1
• Elevated inflammatory markers (CRP, low albumin) 1

Treatment Strategy by Disease Severity

Mild Disease (Ileal or Right Colonic Location)

• Oral budesonide 9 mg once daily for 8 weeks is first-line therapy for mild-to-moderate ileal and/or right colonic Crohn's disease, with efficacy equivalent to prednisolone (51% vs 52.5% remission) but significantly fewer side effects 1, 7, 2, 8
• Evaluate symptomatic response between 4-8 weeks; if inadequate response, escalate to systemic corticosteroids or biologics 1, 7
• Taper budesonide over 1-2 weeks once remission achieved 7
• Budesonide should NOT be used for maintenance therapy as it is ineffective 1

Mild Colonic Disease

• Sulfasalazine 4-6 g/day is suggested for mild Crohn's disease limited to the colon, evaluated for response between 2-4 months 1, 2
• Other 5-ASA products (mesalamine) are NOT recommended as they are ineffective for both induction and maintenance in Crohn's disease 1, 7, 6

Moderate-to-Severe Disease Without High-Risk Features

• Oral prednisone 40-60 mg/day is strongly recommended for moderate-to-severe disease, with evaluation of symptomatic response between 2-4 weeks 1, 7, 6
• If hospitalized, use IV methylprednisolone 40-60 mg/day (typically 40 mg every 8 hours), evaluating response within 1 week 1, 6
• Taper prednisone gradually over 8 weeks once remission achieved, as rapid tapering increases relapse risk 7, 6
• While tapering corticosteroids, immediately initiate maintenance therapy with thiopurines (azathioprine 2-2.5 mg/kg/day or 6-mercaptopurine 1-1.5 mg/kg/day) or methotrexate, as these have 3-6 month onset of action 7, 2, 6

Moderate-to-Severe Disease WITH High-Risk Features

• Anti-TNF biologic therapy (infliximab or adalimumab) with or without immunomodulator should be started immediately as first-line therapy, NOT after corticosteroid failure, as early biologic use achieves higher corticosteroid-free remission rates and prevents disease progression and complications 1, 7, 2, 6
• Combination therapy (anti-TNF plus thiopurine) is more effective than monotherapy for maintaining remission but increases infection risk 7, 6
• Alternative first-line biologics include vedolizumab or ustekinumab, particularly if contraindications to anti-TNF exist 6
• Evaluate response to anti-TNF therapy between 8-12 weeks; if no response by week 14, discontinue and switch to alternative biologic 7, 6

Maintenance Therapy

Critical Principles

• Corticosteroids must NEVER be used for maintenance therapy as they are completely ineffective for maintaining remission and cause significant toxicity 1, 7, 6
• Maintenance therapy is indicated for: patients relapsing >1 time per year, steroid-dependent patients, and those with moderate-to-severe disease or high-risk features at presentation 7

Maintenance Options

• Continue the same biologic agent used for induction indefinitely in responders 6
• Thiopurines (azathioprine 2-2.5 mg/kg/day or 6-mercaptopurine 1-1.5 mg/kg/day) for steroid-dependent patients, with TPMT testing before initiation and regular blood count monitoring 7, 6
• Methotrexate (parenteral 25 mg weekly) as alternative for patients intolerant to thiopurines 7, 6
• Vedolizumab for patients failing corticosteroids, thiopurines, methotrexate, or anti-TNF therapy, with response evaluation at 10-14 weeks 6
• Ustekinumab for moderate-to-severe disease failing other therapies, with response evaluation at 6-10 weeks 6

Monitoring and Follow-Up

Response Assessment Timeline

• Budesonide: evaluate at 4-8 weeks 1, 7
• Prednisone: evaluate at 2-4 weeks 1, 7
• IV methylprednisolone: evaluate within 1 week 1, 6
• Anti-TNF therapy: evaluate at 8-12 weeks, discontinue if no response by week 14 7, 6
• Vedolizumab: evaluate at 10-14 weeks 6
• Ustekinumab: evaluate at 6-10 weeks 6

Objective Monitoring

• Regular monitoring with objective markers (fecal calprotectin, CRP, endoscopy, or cross-sectional imaging) is essential as symptoms poorly correlate with mucosal inflammation 1, 6
• Endoscopic or transmural response should be evaluated within 6 months following initiation of therapy 1
• Consider therapeutic drug monitoring for biologics to optimize dosing and identify patients needing combination therapy 7

Important Caveats

Therapies to AVOID

• Antibiotics are NOT recommended for induction or maintenance of remission in Crohn's disease 1, 8
• Probiotics, omega-3 fatty acids, marijuana, and naltrexone lack evidence for efficacy 6
• Enteral nutrition or dietary modification alone are not suggested for adults (though may have role in pediatrics) 6

Complications Requiring Specific Management

• Before initiating treatment, exclude septic complications (abscesses) that require drainage, strictures causing obstruction, or perforations requiring surgery 1, 5
• Up to 70% of Crohn's disease patients require surgery during their lifetime, with indications including: medically refractory disease, perforation, obstruction, abscess not amenable to drainage, intractable bleeding, or dysplasia 5

Infection Risk

• Patients on high-dose corticosteroids (≥20 mg prednisone daily) require strict infection precautions as this is an established risk factor for opportunistic infections 7
• Combination biologic plus immunomodulator therapy increases infection risk compared to monotherapy 7, 6