What are the common symptoms and treatment options for an adult patient with confirmed Crohn's disease?

Crohn's Disease: Symptoms and Treatment

Common Symptoms

Crohn's disease presents with a constellation of gastrointestinal and systemic symptoms that reflect transmural inflammation affecting any part of the gastrointestinal tract from mouth to perianal region.

Cardinal Gastrointestinal Symptoms

• Chronic diarrhea is a hallmark symptom, with severe flares producing at least 10 loose stools per day 1
• Abdominal pain occurs daily during moderate to severe exacerbations, typically colicky in nature 1
• Weight loss results from both malabsorption and reduced oral intake 1
• Perianal manifestations include anorectal pain, bowel urgency, fecal incontinence, perianal discharge, and tenesmus 1

Systemic Manifestations

• Fever is more common in Crohn's disease flares than in ulcerative colitis 1
• Fatigue and malaise distinguish Crohn's flares from other inflammatory bowel conditions 1
• Anorexia commonly accompanies active disease 2

Laboratory Abnormalities

• Elevated C-reactive protein (CRP) indicates inflammatory burden during flares 1
• Low albumin reflects both inflammation and nutritional status 1
• Anemia is found in 21% of all Crohn's disease patients, most commonly iron deficiency anemia and anemia of chronic disease 3

Disease Distribution

• The terminal ileum and colon are the most commonly affected sites 2
• 25% of patients have colitis only, 25% have ileitis only, and 50% have ileocolitis 4
• The disease can affect the mouth and perianal region 2

Treatment Options

First-Line Therapy for Active Disease

For adults with a first presentation or single inflammatory exacerbation in a 12-month period, conventional glucocorticosteroids (prednisolone, methylprednisolone, or intravenous hydrocortisone) are the recommended first-line therapy to induce remission 2, 5.

• Prednisolone 40 mg daily is appropriate for moderate to severe disease, reduced gradually over 8 weeks 2
• Budesonide 9 mg daily is appropriate for isolated ileocaecal disease with moderate activity, though marginally less effective than prednisolone 2, 5
• Intravenous steroids (hydrocortisone 400 mg/day or methylprednisolone 60 mg/day) are appropriate for severe disease 2

Alternative Induction Therapy

• Enteral nutrition may be considered as an alternative to conventional glucocorticosteroids for children and young people with concerns about growth or side effects 5
• High-dose mesalazine (4 g/daily) may be sufficient for mild ileocolonic disease 2

Add-On Therapy for Recurrent Exacerbations

Add azathioprine or mercaptopurine to conventional glucocorticosteroids or budesonide if there are two or more inflammatory exacerbations in a 12-month period, or if the glucocorticosteroid dose cannot be tapered 5.

• Assess thiopurine methyltransferase (TPMT) activity before offering azathioprine or mercaptopurine 5
• Monitor for neutropenia even in patients with normal TPMT activity 2
• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.25 mg/kg/day are first-line agents for steroid-dependent disease 2

Alternative Immunomodulator

• Methotrexate may be considered for patients who cannot tolerate azathioprine or mercaptopurine, or in whom TPMT activity is deficient 2, 5
• Methotrexate IM 25 mg weekly for up to 16 weeks followed by 15 mg weekly is effective for chronic active disease 2

Biologic Therapy for Moderate-to-Severe Disease

Infliximab and adalimumab are recommended for adults with severe active Crohn's disease whose disease has not responded to conventional therapy (including immunosuppressive and/or corticosteroid treatments), or who are intolerant of or have contraindications to conventional therapy 2, 5.

• Adalimumab dosing for adults: 160 mg on Day 1 (given in one day or split over two consecutive days), 80 mg on Day 15, and 40 mg every other week starting on Day 29 6
• TNF inhibitors (infliximab, adalimumab, certolizumab pegol) are recommended for moderate-to-severe disease unresponsive to conventional therapy 5
• Ustekinumab is recommended for induction of remission in patients with inadequate response to conventional therapy and/or anti-TNF therapy 5
• Upadacitinib may be considered after failure of TNF-alpha inhibitors 5

Maintenance Therapy

Offer azathioprine or mercaptopurine as monotherapy to maintain remission when previously used with a conventional glucocorticosteroid or budesonide to induce remission 2.

• Consider azathioprine or mercaptopurine for maintenance in patients who have not previously received these drugs, particularly those with adverse prognostic factors (early age of onset, perianal disease, glucocorticosteroid use at presentation, severe presentations) 2, 5
• Lifelong maintenance therapy is generally recommended for all patients, especially those with left-sided or extensive disease 2

Surgical Intervention

• Surgery is required in up to two-thirds of CD patients during their lifetime 4
• Common indications include medically refractory disease, perforation, persisting or recurrent obstruction, abscess not amenable to percutaneous drainage, intractable hemorrhage, dysplasia or cancer 4

Critical Pitfalls to Avoid

• Do not assume symptom resolution equals disease control: Inflammation frequently persists without gastrointestinal symptoms, potentially leading to progressive bowel damage even when patients report feeling well 1
• Distinguish strictures from active inflammation: Intestinal obstruction from strictures may mimic a flare but requires different management 1
• Rule out abscess formation: Abscess can present with fever and abdominal pain but needs drainage rather than immunosuppression alone 1
• Monitor for hepatosplenic T-cell lymphoma: This rare but fatal complication occurs primarily in adolescent and young adult males with Crohn's disease receiving TNF blockers concomitantly with azathioprine or 6-mercaptopurine 6
• Screen for tuberculosis: Perform testing for latent TB before initiating TNF blockers; if positive, start TB treatment prior to starting biologic therapy 6

Multidisciplinary Support and Patient Education

• Provide information on smoking cessation, as smoking is a risk factor for disease progression 2, 4
• Discuss fertility and sexual relationships, as these are common concerns 2
• Ensure patients know which symptoms suggest relapse: unintended weight loss, abdominal pain, diarrhea, or general ill-health 2
• Offer age-appropriate multidisciplinary support to address concerns about body image, living with chronic illness, and treatment side effects 2