Introduction
Inflammatory Bowel Disease (IBD) includes two primary conditions, Ulcerative Colitis (UC) and Crohn’s Disease (CD), each characterized by chronic inflammation of the gastrointestinal (GI) tract but differing in their distribution, depth of tissue involvement, and extraintestinal manifestations. UC involves continuous mucosal inflammation limited to the colon and rectum, while CD features a discontinuous, transmural inflammation that can occur anywhere from the mouth to the anus, most commonly affecting the terminal ileum and proximal colon.
Etiology and Pathogenesis
The etiology of IBD is complex and multifactorial, influenced by genetic predispositions, immune dysregulation, environmental triggers, and alterations in the gut microbiome. Key points include:
1. Genetic Susceptibility: Numerous genetic loci have been identified in IBD, particularly for CD. Key genes implicated include NOD2, ATG16L1, IL23R, and STAT3. Genetic markers, such as pANCA (associated with UC) and ASCA (associated with CD), have been noted but are not definitive for diagnosis.
2. Immune Dysregulation: An abnormal immune response to intestinal microbiota is central to IBD pathogenesis. CD primarily involves a Th1 and Th17-mediated response, while UC shows a Th2-skewed response.
3. Environmental Triggers: Factors like smoking, diet, antibiotic use, and sanitation levels are associated with an increased risk of IBD, especially in industrialized countries. Smoking is protective in UC but exacerbates CD.
Clinical Presentation and Diagnosis:
The clinical manifestations vary by disease type, extent, and location:
Ulcerative Colitis (UC):
Symptoms: Bloody diarrhea, urgency, tenesmus, and abdominal pain.
Disease Progression: UC is continuous, starting at the rectum and extending proximally.
Complications: Toxic megacolon, severe bleeding, perforation, and colorectal cancer risk increase with prolonged disease duration.
Crohn’s Disease (CD):
Symptoms: Abdominal pain, weight loss, fatigue, and diarrhea (which may or may not be bloody).
Disease Progression: Features “skip lesions,” where affected and unaffected segments alternate. Transmural inflammation can lead to strictures, fistulas, and abscesses.
Complications: Common complications include intestinal obstruction, fistulas, malabsorption, and perianal disease.
Classification Systems
1. Montreal Classification for Crohn’s Disease: Based on age at diagnosis, location (ileal, colonic, ileocolonic, upper GI), and behavior (inflammatory, stricturing, penetrating).
2. Truelove and Witts Severity Classification for UC: Classifies UC as mild, moderate, severe, or fulminant based on stool frequency, systemic symptoms, and presence of blood. This system aids in assessing the urgency and type of intervention needed.
Diagnostic Workup
A combination of clinical evaluation, imaging, laboratory markers, and endoscopic and histopathological findings is essential for diagnosis:
Endoscopy: Colonoscopy with biopsy remains the gold standard for assessing disease extent and identifying complications like dysplasia. Capsule endoscopy and double-balloon enteroscopy are useful for small bowel CD.
Imaging: CT and MR enterography are critical for evaluating small bowel CD, particularly for assessing complications such as strictures and fistulas.
Histopathology:
UC: Shows mucosal and submucosal inflammation, crypt abscesses, and pseudopolyps.
CD: Features transmural inflammation, granulomas, lymphoid hyperplasia, and fibrosis, with a “cobblestone” appearance on endoscopy due to deep, discontinuous ulcerations.
Laboratory Tests: CRP and fecal calprotectin are useful markers for monitoring disease activity. Autoantibody tests (pANCA, ASCA) may help differentiate UC from CD, though they are not diagnostic.
Pathological Features
Ulcerative Colitis: Characterized by superficial inflammation of the mucosa and submucosa, pseudopolyps, and crypt abscesses. Chronic UC can result in dysplasia and a heightened risk of colorectal cancer.
Crohn’s Disease: Distinguished by deep, transmural inflammation, granulomas, and “creeping fat.” The presence of non-caseating granulomas in biopsy samples is highly indicative but not always present.
Extraintestinal Manifestations
Approximately 30% of IBD patients exhibit extraintestinal symptoms, which may include:
Musculoskeletal: Arthritis, ankylosing spondylitis, and sacroiliitis (particularly associated with UC).
Hepatobiliary: Primary sclerosing cholangitis (PSC) is more common in UC.
Dermatologic: Erythema nodosum and pyoderma gangrenosum.
Ophthalmic: Uveitis and episcleritis.
Complications
Ulcerative Colitis: Major complications include toxic megacolon (with an elevated risk of perforation), severe hemorrhage, and a significant risk of colorectal cancer, particularly in patients with pancolitis or longstanding disease.
Crohn’s Disease: CD may lead to strictures (causing bowel obstruction), fistulas, abscesses, and malabsorption syndromes. Severe disease may also cause systemic amyloidosis due to chronic inflammation.
Treatment Options
Medical Therapy:
Aminosalicylates (5-ASA): First-line for mild-to-moderate UC, primarily acting on mucosal inflammation.
Corticosteroids: Effective for inducing remission in active disease but unsuitable for long-term maintenance due to adverse effects.
Immunomodulators (e.g., azathioprine, methotrexate): Used for steroid-sparing and maintenance in moderate to severe IBD.
Biologics: Anti-TNF agents (infliximab, adalimumab), anti-integrin (vedolizumab), and IL-12/23 inhibitors (ustekinumab) are used for moderate to severe IBD, particularly when other treatments fail.
Novel Agents: JAK inhibitors (e.g., tofacitinib) and S1P receptor modulators (ozanimod) show promise in treatment-resistant cases.
Surgical Intervention:
UC: Surgery is curative for UC, typically involving a total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Indications include refractory disease, severe bleeding, and cancer or dysplasia.
CD: Surgery is not curative for CD. Common procedures include segmental resection, stricturoplasty, and abscess drainage for complications such as strictures and fistulas.
Nutritional Therapy:
Enteral Nutrition: Often preferred in CD for inducing remission and improving nutritional status. Elemental and polymeric diets have shown effectiveness, especially in pediatric patients.
Parenteral Nutrition: Reserved for severe malnutrition or cases where enteral feeding is not feasible.
Cancer Risk and Surveillance
Colorectal Cancer in UC: Long-standing UC, particularly in cases with pancolitis, significantly raises the risk of colorectal cancer. Screening with chromoendoscopy and regular colonoscopies is recommended for early detection of dysplasia.
Intestinal Neoplasms in CD: CD increases the risk of small bowel cancer and, to a lesser degree, colorectal cancer. Surveillance is recommended based on the presence of risk factors like chronic inflammation and previous surgical interventions.
Prognosis and Follow-Up
IBD follows a relapsing-remitting course. Many patients achieve remission with appropriate medical therapy, but a subset may require ongoing, advanced treatments. Regular follow-up with endoscopy, imaging, and monitoring of inflammatory markers (e.g., CRP, fecal calprotectin) is essential for early identification of flares or complications. Long-term care also involves vigilant monitoring for extraintestinal manifestations and cancer screening.
