What are the differential diagnoses, red‑flag features, and recommended work‑up for a patient with recurrent abdominal pain and alternating diarrhea or constipation without obvious structural disease?

Differential Diagnosis of IBS

When a patient presents with recurrent abdominal pain and alternating bowel habits, you must first exclude organic disease through targeted evaluation before diagnosing IBS, focusing on alarm features that signal potentially life-threatening conditions requiring immediate investigation.

Red Flag Features Requiring Full Work-Up

The following alarm features mandate complete evaluation regardless of how typical the IBS symptoms appear 1:

• Age >50 years – requires colonoscopy to exclude colorectal malignancy 1, 2
• Short symptom duration (<6 months) – suggests acute pathology rather than functional disorder 1
• Documented weight loss – indicates possible malignancy, inflammatory bowel disease, or malabsorption 1, 2
• Nocturnal symptoms (pain or diarrhea waking patient from sleep) – distinguishes organic disease from IBS 1, 2
• Rectal bleeding – requires colonoscopy to exclude malignancy or inflammatory bowel disease 1, 2
• Anemia – suggests chronic blood loss or malabsorption 1, 2
• Family history of colon cancer – increases pre-test probability of malignancy 1
• Recent antibiotic use – raises concern for microscopic colitis or C. difficile infection 1

Key Differential Diagnoses to Exclude

Structural/Inflammatory Conditions

• Colorectal cancer – especially in patients >50 years with new-onset symptoms, weight loss, or rectal bleeding 2
• Inflammatory bowel disease (Crohn's disease, ulcerative colitis) – distinguished by nocturnal symptoms, weight loss, and inflammatory markers 2, 3
• Microscopic colitis – requires colonoscopy with biopsies in diarrhea-predominant patients to detect this histologic diagnosis 2
• Celiac disease – test with tissue transglutaminase antibodies in constipation-predominant patients 2
• Appendicitis – right lower quadrant pain requires urgent evaluation before applying IBS criteria 2

Functional/Metabolic Conditions

• Bile acid diarrhea – consider SeHCAT testing or empirical trial of bile acid sequestrant, especially when SeHCAT retention <10% 2
• Hypothyroidism – screen with TSH in constipation-predominant patients 2
• Diabetic autonomic neuropathy – produces nocturnal diarrhea without pain-defecation relationship, unlike IBS 2
• Small intestinal bacterial overgrowth – can mimic IBS but requires specific testing 3

Other Functional Disorders

• Functional constipation – painless bowel dysfunction without abdominal pain 1
• Functional diarrhea – chronic diarrhea without pain 1
• Functional abdominal pain syndrome – continuous pain not relieved by defecation, associated with severe psychological disturbance 1

Recommended Diagnostic Work-Up

Initial Assessment (All Patients)

History must identify 1:

• Pain relieved by defecation
• Pain onset associated with looser or more frequent stools
• Symptom duration >6 months
• Intermittent pattern with flares lasting 2-4 days
• Absence of nocturnal symptoms
• Stress aggravation (though not specific)

Physical examination – must be normal with no abdominal masses, organomegaly, or rectal masses 1, 4

Basic laboratory tests 2:

• Complete blood count (exclude anemia)
• Inflammatory markers (ESR/CRP if inflammatory bowel disease suspected)
• Tissue transglutaminase antibodies (celiac disease screening in constipation-predominant)
• TSH (hypothyroidism screening in constipation-predominant)

Age-Stratified Approach

Patients ≤50 years WITHOUT alarm features 2, 5:

• Can make positive IBS diagnosis based on Rome IV criteria (recurrent abdominal pain ≥1 day/week for 3 months, associated with ≥2 of: pain related to defecation, change in stool frequency, change in stool form)
• No colonoscopy required if symptom duration >2 years and typical presentation

Patients >50 years OR any alarm features 2, 5:

• Mandatory colonoscopy to exclude colorectal cancer and inflammatory bowel disease
• Biopsies during colonoscopy to detect microscopic colitis in diarrhea-predominant patients 2

Subtype-Specific Testing

Diarrhea-predominant 2:

• Sigmoidoscopy or colonoscopy with biopsies (exclude microscopic colitis)
• Consider bile acid malabsorption testing (SeHCAT or empirical bile acid sequestrant trial)
• Stool studies if recent travel or antibiotic use

Constipation-predominant 2:

• TSH (hypothyroidism)
• Tissue transglutaminase antibodies (celiac disease)
• Consider anorectal manometry if pelvic floor dysfunction suspected

Supportive Features That Increase IBS Probability

These features strengthen the diagnosis but are not required 1, 4, 6:

• Female sex – independent predictor of IBS 4, 6
• Age <45 years with >2-year symptom history 6
• Frequent consultations for non-gastrointestinal symptoms 1
• Previous medically unexplained symptoms 1
• Associated conditions: fibromyalgia (20-50% coexist), chronic fatigue syndrome (51%), dyspareunia in women, urinary frequency, lethargy, poor sleep, back pain 4, 6

Common Pitfalls to Avoid

• Do not ignore nocturnal symptoms – these virtually exclude IBS and mandate full organic work-up 2
• Do not skip colonoscopy in patients >50 years – even with typical symptoms, colorectal cancer risk requires exclusion 2
• Do not diagnose IBS in patients with continuous, unremitting pain – this suggests functional abdominal pain syndrome requiring different management 1
• Do not overlook microscopic colitis – requires biopsies during colonoscopy, as endoscopy appears normal 2
• Do not rigidly apply Rome criteria in clinical practice – many genuine IBS patients don't fit exact criteria; use clinical judgment with supportive features 4, 6