Etiologies and Diagnostic Approach to Colitis

Inflammatory Bowel Disease (IBD)

Ulcerative colitis and Crohn’s disease are the primary chronic inflammatory causes of colitis, most commonly affecting young adults (peak age 10‑40 years) and arising from genetic and environmental factors. 1
Ulcerative colitis typically presents with continuous colonic inflammation beginning at the rectum, causing bloody diarrhea, urgency, and tenesmus. 2, 3
Crohn’s disease is characterized by patchy, transmural inflammation that can involve any segment of the gastrointestinal tract, often leading to strictures, fistulas, and perianal disease. 2, 3
Smoking increases the risk of Crohn’s disease but appears protective against ulcerative colitis. 1
“Inflammatory bowel disease unclassified” (formerly indeterminate colitis) accounts for approximately 5‑7 % of IBD cases where diagnostic features overlap. 4, 1

Clostridioides difficile is responsible for about 22 % of infectious colitis cases, especially in patients with recent antibiotic exposure, age > 65 years, hospitalization, or immunosuppression. 5
Infections with Shigella, pathogenic Escherichia coli, and Yersinia species can mimic IBD clinically and endoscopically. 3
Cytomegalovirus (CMV) colitis occurs in immunocompromised hosts (e.g., HIV, post‑transplant) and may super‑infect existing IBD, producing a spectrum of endoscopic findings from patchy erythema to deep ulcers. 2, 3

Ischemic colitis typically presents with sharply demarcated colonic segments, petechial hemorrhages, and longitudinal ulcerations. 2
Cross‑sectional imaging has a sensitivity of 53‑85 % and specificity of 75‑78 % for ischemic colitis and cannot reliably differentiate it from other colitides. 6

Immune checkpoint inhibitor (ICI)‑related colitis occurs in patients receiving PD‑1/PD‑L1 or CTLA‑4 blockers; approximately 95 % show left‑sided inflammation on biopsy. 6
Stool lactoferrin or calprotectin testing (≈ 90 % sensitivity) helps identify patients who require endoscopic evaluation for suspected ICI colitis. 6
Flexible sigmoidoscopy is usually sufficient for diagnosing ICI colitis because of its predominant left‑sided distribution. 6
Isolated upper‑GI inflammation is observed in more than 10 % of ICI colitis cases. 6
Non‑steroidal anti‑inflammatory drugs (NSAIDs), proton‑pump inhibitors, and selective serotonin reuptake inhibitors can trigger or worsen colitis and should be discontinued in refractory microscopic colitis. 7

Microscopic colitis (collagenous and lymphocytic subtypes) predominantly affects adults ≥ 60 years, with a prevalence of 48‑219 per 100 000, presenting as chronic watery, non‑bloody diarrhea despite a normal endoscopic appearance. 7
Diagnosis relies on histology: a thickened subepithelial collagen band (collagenous) or increased intra‑epithelial lymphocytes (lymphocytic). 8, 4
The condition is associated with autoimmune diseases and exposure to certain medications. 7
Microscopic colitis does not increase colorectal cancer risk and does not typically require surgical intervention. 7

Routine microbiologic work‑up—including stool culture, C. difficile testing, and multiplex PCR—should be performed at initial presentation and during disease flares, as bacterial superinfection can precipitate IBD exacerbations. 8, 4
Histology alone cannot reliably exclude bacterial infection, particularly C. difficile infection. 8, 4
Pre‑operative biopsies should avoid labeling cases as “indeterminate colitis”; the preferred terminology is “IBD unclassified.” 4
Computed tomography has a low negative predictive value for suspected ICI colitis and should be reserved for complications such as pain, fever, or bleeding rather than isolated diarrhea. 6
When the diagnosis remains uncertain, scheduled follow‑up endoscopy at 1 year and 5 years is recommended, as most ambiguous cases ultimately behave like ulcerative colitis. 8

Microscopic colitis usually shows a completely normal or near‑normal colonic mucosa on colonoscopy, making histologic biopsy essential for diagnosis despite the lack of visible lesions. 9

Biopsies should be taken from multiple colonic segments rather than relying solely on rectal samples to ensure adequate diagnostic yield. 9
When only flexible sigmoidoscopy is performed, additional biopsies from the descending colon (in addition to rectosigmoid segments) are recommended. 9

Microscopic colitis is identified in approximately 3.7 %–7.5 % of patients evaluated for chronic watery diarrhea. 9