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

Symptoms of Crohn's Disease

Crohn's disease presents with abdominal pain, diarrhea, and weight loss as the cardinal gastrointestinal symptoms, with the terminal ileum and colon being the most commonly affected sites. 1, 2

Primary Gastrointestinal Symptoms

• Abdominal pain is a hallmark symptom, reflecting transmural inflammation that can occur anywhere from mouth to anus 1, 3
• Diarrhea occurs frequently and may be chronic or intermittent depending on disease activity 1, 2
• Weight loss results from malabsorption, reduced intake due to pain, and the inflammatory process itself 1, 3
• Rectal bleeding may occur, particularly when colonic disease is present 4
• Fever can accompany active inflammatory exacerbations 3, 4

Disease Distribution Patterns

• The terminal ileum and colon are most commonly affected, with approximately 50% of patients having ileocolonic disease, 25% having isolated colitis, and 25% having isolated ileitis 1, 5
• The disease can affect the entire gastrointestinal tract, including the mouth and perianal region 1, 2
• Perianal manifestations include skin tags, fissures, fistulas, and abscesses 1

Extraintestinal Manifestations

• Musculoskeletal: inflammatory arthropathies and osteoporosis 3
• Ocular: scleritis and uveitis 3
• Dermatologic: erythema nodosum 3
• Hepatobiliary: cholelithiasis 3
• Renal: nephrolithiasis 3

Disease Course Characteristics

• Crohn's disease follows a chronic relapsing-remitting course with periods of clinical remission alternating with inflammatory exacerbations 1, 2
• Approximately 50% of patients experience a relapse in any given year 2
• The disease is associated with considerable debility and significant impact on quality of life, including psychological morbidity in both children and adults 1, 2

Complications and Advanced Disease Features

• Stricture formation develops in many patients over time, causing obstructive symptoms 1
• Fistulizing disease includes enterocutaneous and rectovaginal fistulas 1
• Abdominal masses may be palpable on examination 3
• Anemia commonly develops from chronic inflammation, blood loss, or nutritional deficiencies 3, 4
• Up to one-third of patients present with complicated behavior (strictures, fistulas, abscesses) at diagnosis 6

Pediatric-Specific Concerns

• Delayed growth and puberty may occur in children and young people with Crohn's disease 1
• Growth concerns should prompt consideration of enteral nutrition as an alternative to corticosteroids 1

Symptoms Suggesting Relapse

When patients are in remission and not on maintenance therapy, they should be counseled that the following symptoms warrant immediate consultation 1:

• Unintended weight loss
• Abdominal pain (new or worsening)
• Diarrhea (recurrent or persistent)
• General ill-health or malaise

Treatment Overview

Induction of Remission

• Conventional glucocorticosteroids (prednisolone, methylprednisolone, or IV hydrocortisone) are first-line therapy for initial presentation or single inflammatory exacerbation 1, 6, 7
• Budesonide 9 mg/day is recommended for mild to moderate distal ileal, ileocaecal, or right-sided colonic disease 6, 7
• Prednisone 40-60 mg/day is strongly recommended for moderate to severe disease, with gradual tapering over 8 weeks 6
• Enteral nutrition may be considered as an alternative to corticosteroids in children with growth concerns 1, 7

Add-on Therapy for Steroid-Dependent Disease

• Azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day should be added if there are two or more inflammatory exacerbations in 12 months or if corticosteroid dose cannot be tapered 1, 7
• Methotrexate (15-25 mg IM weekly) is an alternative for patients who cannot tolerate azathioprine/mercaptopurine or have deficient TPMT activity 1, 7
• TPMT activity must be assessed before offering azathioprine or mercaptopurine 1, 7

Biologic Therapy

• Infliximab and adalimumab are recommended for severe active Crohn's disease that has not responded to conventional therapy or when patients are intolerant of conventional therapy 1, 8, 9
• These agents should be given as a planned course until treatment failure or 12 months after start of treatment, whichever is shorter 1
• Vedolizumab is recommended for patients who fail corticosteroids, thiopurines, methotrexate, or anti-TNF therapy 6
• Ustekinumab is recommended for moderate to severe disease after failure of other therapies 6, 7

Maintenance of Remission

• Azathioprine or mercaptopurine should be offered as monotherapy when previously used with corticosteroids to induce remission 1, 6
• Consider these agents in patients with adverse prognostic factors such as early age of onset, perianal disease, glucocorticosteroid use at presentation, and severe presentations 1
• Methotrexate should be considered only in patients who needed it for induction, cannot tolerate azathioprine/mercaptopurine, or have contraindications to these agents 1, 6
• Patients who respond to biologic therapy should continue the same agent for maintenance 6
• Corticosteroids should never be used for maintenance therapy 1, 6

Fistulizing and Perianal Disease

• Metronidazole 400 mg three times daily and/or ciprofloxacin 500 mg twice daily are first-line treatments for simple perianal fistulae 1
• Infliximab (three infusions of 5 mg/kg at 0,2, and 6 weeks) is effective for reducing draining fistulas and maintaining fistula closure in refractory cases 1, 7, 8
• Surgical options include seton drainage, fistulectomy, and advancement flaps in combination with medical treatment 1

Surgical Management

• 18-31% of patients require intestinal resection within 5 years of diagnosis, and 25-40% within 10 years 1
• Surgery should be deferred when possible to allow multimodal optimization including nutrition, corticosteroid weaning, and abscess management 1
• Strictureplasty is an alternative to resection for small bowel strictures shorter than 10 cm and is useful for preserving gut length 1

Important Monitoring Considerations

• Monitor for neutropenia in patients taking azathioprine or mercaptopurine, even with normal TPMT activity 1
• Follow BNF/BNFC guidance on monitoring immunosuppressives 1
• Smoking cessation is the most important factor in maintaining remission and should be strongly advised 1
• Regular monitoring with objective markers (endoscopy, CRP, calprotectin, imaging) is crucial due to disconnect between symptoms and inflammation 6

Common Pitfalls

• Do not use mesalamine at doses less than 2 g/day or for patients who needed steroids to induce remission, as it has limited benefit 1
• Avoid sulfasalazine for maintenance, as it is not effective 1
• Do not use long-term opioids, as they are associated with poor outcomes 6
• Probiotics, omega-3 fatty acids, marijuana, and naltrexone are not recommended for inducing or maintaining remission 6