What are the symptoms and treatment options for Crohn's disease?

Crohn's Disease Symptoms and Treatment

Clinical Presentation

Patients with Crohn's disease present with a constellation of gastrointestinal and systemic symptoms that vary based on disease severity and location. 1

Intestinal Symptoms

• Chronic diarrhea (at least 10 loose stools daily in severe disease) is the hallmark symptom 1
• Daily abdominal pain occurs frequently, particularly in moderate to severe disease 1
• Rectal bleeding may be present, especially with colonic involvement 2
• Unintended weight loss and anorexia are common systemic manifestations 1
• Fatigue affects most patients with active disease 2

Perianal Manifestations

• Anorectal symptoms including pain, bowel urgency, incontinence, discharge, and tenesmus indicate perianal disease involvement 1
• Perianal fistulas and abscesses occur in a significant proportion of patients 1

Extraintestinal Manifestations

• Musculoskeletal: Joint involvement occurs in 20-25% of patients, presenting as peripheral arthropathy or axial arthropathy (ankylosing spondylitis) 3
• Dermatologic: Erythema nodosum (parallels disease activity) and pyoderma gangrenosum (independent course) 3
• Ophthalmologic: Uveitis/iritis requiring urgent ophthalmology referral to prevent vision loss 3
• Hematologic: Anemia affects 21% of patients, with iron deficiency being most common 3

Disease Severity Classification

The Crohn's Disease Activity Index (CDAI) stratifies severity: remission <150, mild-to-moderate 150-220, moderate-to-severe 220-450, and severe >450 1. Severe disease is characterized by large/deep mucosal lesions, fistulas, strictures, extensive disease (>40cm ileal involvement or pancolitis), anemia, elevated C-reactive protein, and low albumin 1.

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Treatment Algorithm

Mild-to-Moderate Disease (First Presentation or Single Exacerbation)

Conventional glucocorticosteroids (prednisolone 40mg daily) are first-line therapy for initial presentation or single inflammatory exacerbation, tapered gradually over 8 weeks. 1, 4

• Budesonide 9mg daily is appropriate for isolated ileocecal disease with moderate activity, though marginally less effective than prednisolone 1, 4
• High-dose mesalazine (4g daily) may be sufficient for mild ileocolonic disease 1
• Sulfasalazine 4g daily is effective for colonic disease but has high side effect incidence 1
• Enteral nutrition (elemental or polymeric diets) is an alternative for children and patients declining steroids 1, 4

Moderate-to-Severe Disease Requiring Escalation

Add azathioprine or mercaptopurine to glucocorticosteroids if there are ≥2 inflammatory exacerbations in 12 months or if the steroid dose cannot be tapered. 1, 4

• Assess thiopurine methyltransferase (TPMT) activity before initiating azathioprine or mercaptopurine 1, 4
• Methotrexate is the alternative if patients cannot tolerate thiopurines or have deficient TPMT activity 1, 4
• Monitor for neutropenia in all patients taking azathioprine/mercaptopurine, even with normal TPMT 1

Severe Disease or Conventional Therapy Failure

TNF inhibitors (infliximab, adalimumab, certolizumab pegol) are recommended for moderate-to-severe disease that has not responded to conventional therapy or when patients are intolerant/have contraindications. 1, 4, 5, 6

• Infliximab: 5mg/kg IV at weeks 0,2,6, then every 8 weeks; may increase to 10mg/kg if response is lost 5
• Adalimumab: 160mg day 1, 80mg day 15, then 40mg every other week starting day 29 6
• Ustekinumab (IL-12/23 antagonist) is recommended for patients with inadequate response to conventional therapy and/or anti-TNF therapy 4
• Vedolizumab (anti-integrin) and upadacitinib (JAK inhibitor) provide additional options after TNF inhibitor failure 4
• Biologics should be given as planned courses until treatment failure or 12 months, then reassessed 1

Fistulizing Disease

Infliximab is the most effective therapy for perianal fistulizing disease, both for reducing draining fistulas and maintaining fistula closure. 4, 5

• Metronidazole and ciprofloxacin can be used for simple perianal fistulas 3
• Noncutting setons are the surgical treatment of choice for high fistulas with active rectal inflammation 1
• Treat any active proximal luminal disease with appropriate medications (budesonide, corticosteroids, azathioprine, methotrexate, or infliximab) 4

Maintenance Therapy

Offer azathioprine or mercaptopurine as monotherapy to maintain remission when previously used with glucocorticosteroids to induce remission. 1

• Consider azathioprine/mercaptopurine for maintenance in patients with adverse prognostic factors (early age of onset, perianal disease, glucocorticosteroid use at presentation, severe presentations) 1, 4
• Methotrexate for maintenance only if used to induce remission or if thiopurines were not tolerated 1
• Continue biologic therapy as maintenance if used for induction (except corticosteroids) 1

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Critical Monitoring and Safety Considerations

Laboratory Monitoring

• Monitor FBC, ESR/CRP, electrolytes, albumin, and liver function every 24-48 hours during severe disease 1
• Follow BNF/BNFC guidance for monitoring immunosuppressives (azathioprine, mercaptopurine, methotrexate) 1
• Screen for latent tuberculosis before initiating TNF inhibitors and monitor during therapy 5, 6

Serious Infection Risk

Patients on TNF inhibitors are at increased risk for serious infections including tuberculosis reactivation, invasive fungal infections (histoplasmosis, coccidioidomycosis), and opportunistic infections. 5, 6

• Discontinue biologics if serious infection or sepsis develops 5, 6
• Consider empiric antifungal therapy in at-risk patients who develop severe systemic illness 5

Malignancy Risk

Lymphoma and hepatosplenic T-cell lymphoma (HSTCL) have been reported, particularly in adolescent and young adult males receiving TNF blockers with concomitant azathioprine or 6-mercaptopurine. 5, 6

Thromboembolism Prevention

• Subcutaneous heparin should be given to reduce thromboembolism risk during severe disease 1
• Patients with Crohn's disease have increased risk of venous thromboembolism requiring vigilance during hospitalizations 3

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Common Clinical Pitfalls

Never assume all arthropathy will improve with intestinal disease treatment alone—Type II peripheral arthropathy and axial arthropathy require specific rheumatologic management independent of bowel disease control 3.

Do not delay surgical consultation in patients with severe disease, as joint medical-surgical management improves outcomes; historically 24% required surgery within one year of diagnosis 1.

Recognize that patients with one extraintestinal manifestation are at increased risk for developing additional manifestations, requiring heightened surveillance 3.

Screen all patients routinely for anemia (present in 21% of patients) and nutritional deficiencies 3.

Counsel all patients on smoking cessation, as smoking is a significant modifiable risk factor 1, 2.