What is the differential diagnosis and management approach for a patient with chronic gastroenteritis, considering factors such as age, travel history, and family history of inflammatory bowel disease (IBD)?

Differential Diagnosis for Chronic Gastroenteritis

The differential diagnosis for chronic gastroenteritis must systematically exclude inflammatory bowel disease (IBD), celiac disease, infectious causes (particularly Giardia), bile acid diarrhea, and functional disorders like IBS-D, with the diagnostic approach prioritizing fecal calprotectin screening, celiac serology, stool testing for Giardia, and colonoscopy with biopsies when indicated.

Primary Diagnostic Considerations

Inflammatory Bowel Disease (IBD)

• IBD (Crohn's disease or ulcerative colitis) is the most critical diagnosis to exclude given its implications for long-term morbidity and need for immunosuppressive therapy 1, 2.
• Family history of IBD significantly increases pre-test probability and should lower the threshold for invasive testing 1, 3.
• Fecal calprotectin >250 μg/g warrants urgent gastroenterology referral and colonoscopy, while values 100-250 μg/g require repeat testing or routine referral depending on clinical suspicion 1.
• Fecal calprotectin or fecal lactoferrin should be used to screen for IBD rather than ESR or CRP, as these have superior diagnostic accuracy 1.
• Colonoscopy to the terminal ileum with multiple biopsies (at least 2 from terminal ileum, 4 from different colonic segments, and 2 from rectum) is essential when IBD is suspected 1, 2.

Celiac Disease

• Testing for celiac disease with IgA tissue transglutaminase (tTG) plus a second test to detect IgA deficiency is mandatory in all patients with chronic diarrhea 1.
• IgA-tTG has >90% sensitivity and specificity using thresholds of 7-15 AU/mL 1.
• Positive serology requires confirmation with duodenal biopsy 1.

Infectious Causes

• Giardia testing is strongly recommended in all patients with chronic diarrhea regardless of travel history 1.
• Stool testing for ova and parasites (other than Giardia) should only be performed in patients with travel history to or recent immigration from high-risk areas 1.
• Clostridioides difficile testing is essential in patients with recent antibiotic exposure or hospitalization 1, 4.
• Consider testing for amoebic dysentery or Shigella in patients with relevant travel history 1.
• Post-infectious IBS develops in approximately 9% of patients after acute gastroenteritis and accounts for >50% of all IBS cases 4, 5.

Bile Acid Diarrhea

• Bile acid diarrhea should be considered, particularly in patients with terminal ileal resection or disease 1.
• Testing options include 48-hour stool bile acid collection or serum fibroblast growth factor 19, though these tests have limited availability 1.
• An empiric trial of bile acid sequestrants is reasonable when bile acid diarrhea is suspected, as diagnostic tests are not widely available 1.

Functional Disorders (IBS-D)

• IBS-D is a major cause of chronic watery diarrhea but remains a diagnosis of exclusion 1.
• Currently available serologic tests for IBS (antibodies to cytolethal distending toxin B and vinculin) lack sufficient diagnostic accuracy for routine use, with sensitivity only 20-40% 1.
• Fecal calprotectin <100 μg/g makes IBS more likely and supports treatment as IBS in primary care 1.

Age-Specific Considerations

Younger Patients (16-40 years)

• IBD is more likely in this age group, particularly with family history 1, 3.
• Consider genetic testing for monogenic disorders if symptoms began before age 5 years or presentation is particularly aggressive 3.

Older Patients (>60 years)

• Colorectal cancer, colonic diverticula, angiodysplasia, ischemic colitis, NSAID-induced pathology, radiation colitis, and microscopic colitis become more prevalent 6.
• Lower threshold for colonoscopy given increased cancer risk 6.

Critical Clinical Features Requiring Urgent Evaluation

Alarm Features

• Unexplained weight loss, persistent rectal bleeding, nocturnal diarrhea, or new-onset symptoms in patients >40 years warrant urgent investigation 1.
• Abdominal, rectal, or anal mass or unexplained anal ulceration requires referral via suspected cancer pathway 1.
• Systemic symptoms (fever, malaise, anorexia) are more common in Crohn's disease 2, 3.

Systematic Diagnostic Algorithm

Initial Primary Care Assessment

1. Complete blood count, comprehensive metabolic panel, CRP, and celiac serology should be obtained first 1, 2, 3.
2. Fecal calprotectin measurement (not appropriate if NSAID use in past 6 weeks) 1:
   • <100 μg/g: IBS likely, treat in primary care
   • 100-250 μg/g: Consider repeat testing or routine gastroenterology referral

   • 250 μg/g: Urgent gastroenterology referral

3. Stool culture for bacterial pathogens and C. difficile if infectious etiology suspected 1, 2.
4. Giardia-specific testing in all cases 1.

Secondary Care Evaluation

• Colonoscopy with terminal ileal intubation and multiple segmental biopsies is the gold standard when organic disease is suspected 1, 2, 3.
• Biopsies must be placed in separate containers to map inflammation distribution, which increases diagnostic accuracy from 66% to 92% 3.
• Upper endoscopy with duodenal biopsies if celiac serology is positive or upper GI symptoms are present 1.
• Cross-sectional imaging (MR enterography preferred over CT) for suspected small bowel Crohn's disease, obstructive symptoms, or complications 2, 3.

Additional Differential Diagnoses to Consider

Microscopic Colitis

• More common in older patients and those on NSAIDs 1, 6.
• Requires colonic biopsies for diagnosis as endoscopy appears normal 1.

Small Intestinal Bacterial Overgrowth (SIBO)

• Consider in patients with previous gastric or intestinal surgery, particularly bypass procedures 1, 3.

Endocrine Causes

• Thyrotoxicosis, diabetes mellitus with autonomic dysfunction, and adrenal disease can cause chronic diarrhea 1.

Drug-Induced Diarrhea

• NSAIDs, antibiotics, and other medications must be reviewed 1.

Common Pitfalls to Avoid

• Do not rely on ESR or CRP alone to screen for IBD—fecal calprotectin is superior 1.
• Do not perform broad ova and parasite testing without travel history—test specifically for Giardia instead 1.
• Do not diagnose IBS without excluding organic disease, particularly in patients with alarm features or elevated fecal calprotectin 1.
• Do not assume normal inflammatory markers exclude IBD—approximately 20% of active Crohn's disease patients have normal CRP 3.
• Fecal calprotectin can be falsely elevated with NSAID use in the past 6 weeks 1.
• Previous gastroenteritis increases odds of later IBD development (OR 2.4), with highest risk in the first year post-infection (OR 4.1), particularly with Salmonella, Campylobacter, E. coli, or C. difficile 7, 8, 9.