What are the key differences between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) regarding pathology, diagnostic work‑up, red‑flag features, and treatment?

IBD vs IBS: Key Differences

IBD and IBS are fundamentally distinct conditions—IBD is characterized by chronic intestinal inflammation with structural damage visible on endoscopy and histology, while IBS is a disorder of gut-brain interaction diagnosed by symptom criteria without inflammatory markers or structural abnormalities. 1

Pathology

IBD (Inflammatory Bowel Disease)

• Chronic mucosal and/or transmural inflammation with detectable structural abnormalities on endoscopy and histology 1, 2
• Ulcerative colitis shows continuous mucosal inflammation limited to the colon, while Crohn's disease demonstrates transmural, skip-lesion inflammation that can affect any part of the GI tract 1
• Histologic features include crypt architectural distortion, basal plasmacytosis, and chronic inflammatory infiltrates 1
• Persistent immune activation with elevated inflammatory markers (elevated fecal calprotectin, CRP, ESR) 3

IBS (Irritable Bowel Syndrome)

• No structural abnormalities or inflammation detectable by standard endoscopy and histology 1, 4
• Disorder of gut-brain interaction with altered visceral sensitivity, motility disturbances, and microbiota changes 1, 2
• Some patients show subtle "microinflammation" with increased mast cells and intraepithelial lymphocytes, but this does not meet criteria for IBD 3, 2
• Normal inflammatory markers (normal fecal calprotectin) 3

Diagnostic Work-Up

For IBD

• Endoscopy with biopsies is essential to visualize mucosal inflammation and obtain histologic confirmation 1
• Multiple biopsies from different segments of colon, ileum, and other GI tract areas are required 1
• Fecal calprotectin elevated (helps distinguish from IBS) 3
• Laboratory markers: anemia, elevated CRP/ESR, thrombocytosis 1
• Imaging (CT/MRI enterography) to assess extent and complications 1

For IBS

• Positive symptom-based diagnosis using Rome IV criteria: recurrent abdominal pain (≥1 day/week in last 3 months) related to defecation, associated with change in stool frequency and/or form 1
• Limited investigations to exclude organic disease: CBC, CRP, fecal calprotectin, celiac serology, colonoscopy only if alarm features present 1
• Normal endoscopy and histology if performed 1, 4
• Subtype classification based on stool consistency: IBS-D (loose >25% time), IBS-C (hard >25% time), IBS-M (both >25% time) 1, 5

Red-Flag Features

Alarm Features Requiring Investigation (Suggest IBD, Not IBS)

• Age >50 years at symptom onset 1, 6
• Rectal bleeding or blood in stool 1, 6
• Unintentional weight loss 1, 6
• Nocturnal symptoms that wake patient from sleep (IBS symptoms typically subside during sleep) 1, 5, 6
• Fever 1, 6
• Family history of colon cancer or IBD 1
• Anemia 1
• Short history of symptoms (<6 months) 1
• Persistent vomiting 5, 6

IBS-Supportive Features (When Alarm Features Absent)

• Symptoms present >6 months 1
• Intermittent symptoms with flares lasting 2-4 days followed by remission 1, 5
• Patient reports stress aggravates symptoms 1
• Frequent consultations for non-GI symptoms 1
• Symptoms resolve during sleep 5

Treatment Approaches

IBD Treatment

• Immunosuppressive and anti-inflammatory therapy targeting mucosal inflammation: corticosteroids, immunomodulators (azathioprine, methotrexate), biologics (anti-TNF, anti-integrin, anti-IL-12/23) 1
• Goal is mucosal healing with resolution of inflammation 1
• Surgery for complications (strictures, fistulas, refractory disease) 7
• Monitoring with endoscopy and inflammatory markers 1

IBS Treatment

• Symptom-directed therapy without immunosuppression 1
• For IBS-D: loperamide, ondansetron, ramosetron, eluxadoline, rifaximin 5, 6
• For IBS-C: soluble fiber, osmotic laxatives (polyethylene glycol), linaclotide, lubiprostone 5
• For IBS-M: SSRIs, rifaximin, psychological therapy (CBT, hypnotherapy), antispasmodics 1, 5, 6
• Dietary modifications: low FODMAP diet, lactose reduction, gluten-free diet 1
• Psychological interventions: cognitive behavioral therapy, gut-directed hypnotherapy 1

Critical Pitfalls to Avoid

Do not treat persistent symptoms in IBD patients with escalating immunosuppression without first excluding functional overlap—up to 39% of IBD patients in remission have coexisting IBS-type symptoms that will not respond to anti-inflammatory therapy 1. Verify mucosal healing with endoscopy and normal fecal calprotectin before attributing symptoms to active IBD 1.

Do not dismiss alarm features in presumed IBS patients—rectal bleeding, weight loss, nocturnal symptoms, age >50 at onset, or anemia mandate endoscopic evaluation to exclude IBD or malignancy 1, 6.

Fecal calprotectin is the key discriminator when symptoms overlap—elevated levels indicate IBD activity, while normal levels support IBS or functional symptoms in IBD remission 3.

Recognize that IBS in IBD patients may indicate more severe disease—patients with concomitant IBD and IBS have higher rates of complications (perforation, bleeding, abscess) and surgical interventions than IBD patients without IBS symptoms 7.