What is inflammatory bowel disease (IBD)?

What is Inflammatory Bowel Disease?

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders of the gastrointestinal tract, most commonly comprising ulcerative colitis (UC) and Crohn's disease (CD), which result from an overly aggressive mucosal immune response against luminal bacteria in genetically susceptible individuals. 1

Core Disease Entities

Crohn's Disease

• Transmural inflammation that can affect any part of the gastrointestinal tract from mouth to anus, with the terminal ileum and colon being the most common sites 1
• Characterized by patchy, discontinuous ("skip") lesions with areas of normal bowel between inflamed segments 1
• Complications include strictures, fistulas, and abscesses due to the transmural nature of inflammation 1
• Endoscopic features include aphthous ulcers, longitudinal ulcers, and cobblestone appearance 2
• Histopathology shows focal chronic inflammation, small non-caseating granulomas, and crypt architectural distortion 2

Ulcerative Colitis

• Mucosal inflammation limited to the colon that typically starts distally in the rectum and progresses proximally in a continuous pattern 1
• The cardinal symptom is bloody diarrhea, often accompanied by colicky abdominal pain, urgency, and tenesmus 1
• Disease extent ranges from proctitis (rectum only) to pancolitis (entire colon) 1
• Ileal involvement is rare, occurring as "backwash ileitis" in approximately 20% of patients with extensive colitis 3, 2
• Endoscopic features include loss of vascular pattern, granularity, friability, and ulceration of the rectal mucosa 1

Epidemiology and Demographics

• Highest prevalence in Europe (UC: 505 per 100,000 in Norway; CD: 322 per 100,000 in Germany) and North America (UC: 286 per 100,000 in USA; CD: 319 per 100,000 in Canada) 1
• Prevalence exceeds 0.3% in North America, Oceania, and many European countries 1
• Peak incidence occurs between ages 10-40 years, though 15% of patients are diagnosed after age 60 1
• Incidence is stable or decreasing in Western countries but rising in newly industrialized countries in Africa, Asia, and South America since 1990 1
• CD shows female predominance in Western populations but male predominance in Eastern populations, while UC shows no consistent gender difference 1

Clinical Presentation

Common Symptoms

• Abdominal pain, diarrhea (bloody in UC, non-bloody more common in CD), vomiting, rectal bleeding, weight loss, and anemia 1
• Systemic symptoms including malaise, anorexia, and fever are more common in CD than UC 1
• CD presents more heterogeneously than UC due to variable location and pattern of disease 1

Extra-intestinal Manifestations

• Arthritis (most common extra-intestinal manifestation, occurring in approximately 15% of IBD patients) 1
• Skin disorders and uveitis 1
• These manifestations may precede intestinal symptoms in about 25% of patients 1

Pathogenesis

• Multifactorial etiology involving environmental triggers, genetic susceptibility, dysregulated immune response, and abnormal gut microbiota 1, 4
• Smoking increases risk of CD but decreases risk of UC through unknown mechanisms 1
• Genetic component is stronger in CD than UC, with CARD15/NOD2 gene mutations associated with small intestinal CD in white populations 1
• Chronic intestinal inflammation originates from an overly aggressive mucosal immune response against luminal bacteria 1

Diagnosis

• Confirmed by clinical evaluation combined with biochemical markers, endoscopy with histology, and radiology 1
• For UC: diagnosis requires clinical suspicion, appropriate macroscopic findings on sigmoidoscopy/colonoscopy, typical histological findings, and negative stool examinations for infectious agents 1
• For CD: diagnosis depends on demonstrating focal, asymmetric, and often granulomatous inflammation 1
• Ileocolonoscopy with multiple biopsies is the gold standard for diagnosis 3, 2
• Initial laboratory investigations should include complete blood count, inflammatory markers (ESR, CRP, fecal calprotectin), liver function tests, and stool cultures for infectious pathogens including C. difficile 1, 2

Disease Course and Prognosis

Ulcerative Colitis

• Clinical course marked by exacerbations and remissions, with approximately 50% of patients experiencing a relapse in any given year 1
• Overall, 20-30% of patients with pancolitis require colectomy 1
• Slight excess mortality in the first two years after diagnosis, but little subsequent difference from normal population 1
• After the first year, approximately 90% of patients are fully capable of work 1

Crohn's Disease

• At least 50% of patients require surgical treatment within the first 10 years of disease, and 70-80% will require surgery within their lifetime 1
• Surgery is not curative in CD, and disease tends to recur 1
• Overall mortality is slightly higher than the normal population, greatest in the first 2 years after diagnosis or in those with upper gastrointestinal disease 1
• CD causes greater disability than UC, with only 75% of patients fully capable of work in the year after diagnosis and 15% unable to work after 5-10 years 1

Treatment Principles

• Management aims to achieve induction of remission followed by maintenance therapy to prevent recurrent disease flares 1
• Treatment is tailored based on disease type, distribution, severity, comorbidities, and patient preferences 1
• Conventional immunosuppressive therapies include azathioprine, 6-mercaptopurine, methotrexate, and 6-thioguanine 1
• Biologics (anti-TNF agents like infliximab, adalimumab, golimumab; anti-integrin vedolizumab; anti-IL-12/23 ustekinumab) are used for insufficient response to immunosuppression or intolerance 1
• JAK inhibitor tofacitinib is approved for UC treatment 1
• A treat-to-target approach is recommended, involving iterative treatment adjustments to achieve clinical response, reduce inflammatory markers, and achieve mucosal healing 5

Socioeconomic Impact

• IBD is chronic and potentially disabling, frequently leading to hospitalizations, lower quality of life, and inability to work 1
• Substantial socioeconomic impact with significant employment problems for a minority of patients 1
• Both UC and Crohn's colitis are associated with increased risk of colonic carcinoma 1