Differential Diagnosis for Acute Gastroenteritis
When evaluating acute gastroenteritis, prioritize ruling out infectious colitis, inflammatory bowel disease (IBD), ischemic colitis, and C. difficile infection based on specific clinical features, with faecal calprotectin >250 μg/g warranting urgent gastroenterology referral to exclude IBD. 1
Initial Clinical Assessment and Red Flags
Immediate evaluation priorities:
- Severe dehydration (≥10% fluid deficit) identified by prolonged skin tenting >2 seconds, altered mental status, cool extremities with poor capillary refill, and rapid deep breathing indicating acidosis requires immediate IV resuscitation 2
- Bloody stools with fever and systemic toxicity suggest bacterial dysentery (Salmonella, Shigella, enterohemorrhagic E. coli) or IBD and mandate stool cultures, flexible sigmoidoscopy with biopsy, and consideration of hemolytic uremic syndrome monitoring 1, 3
- Recent antibiotic exposure necessitates immediate C. difficile testing via PCR or toxin assay, as IBD patients have increased risk for C. difficile with subsequent hospitalization and colectomy 1, 4
- Signs of sepsis (hypotension, tachycardia, altered mental status) require blood cultures, immediate IV fluid resuscitation, and consideration of surgical abdomen 1
Differential Diagnosis Framework
High-Priority Conditions to Rule Out
Inflammatory Bowel Disease (IBD):
- Faecal calprotectin is the key screening tool with high negative predictive value for ages 16-40 presenting with chronic diarrhea 1
- Clinical features favoring IBD over infection: Rectal bleeding plus abdominal pain, change in bowel habit, weight loss, or iron deficiency anemia 1
- Endoscopic features of IBD: Anorectal lesions, longitudinal and aphthous ulcers, cobblestone appearance, continuous inflammation from rectum proximally in UC 1
- Flexible sigmoidoscopy with biopsy is essential in acute severe colitis for diagnosis and excluding other causes; colonoscopy should be avoided in acute setting due to perforation risk 1
Infectious Colitis:
- Bacterial causes (38% of acute hemorrhagic colitis): Salmonella, Shigella, Campylobacter, enteroinvasive/enterohemorrhagic E. coli, Yersinia, C. difficile 1, 3
- Multiplex antimicrobial testing is preferred over traditional stool cultures and microscopy 4
- Endoscopic differentiation: Patulous ileocecal valve, transverse ulcers, and scar/pseudopolyp favor intestinal tuberculosis over Crohn's disease 1
- Viral causes (most common): Norovirus (58% of hospitalized children), rotavirus 5, 4
- Parasitic causes: Giardia (particularly in daycare settings) 5
Ischemic Colitis:
- Clinical clues: Normal rectum, sharply defined segments involving "watershed territory" (sigmoid to splenic flexure), petechial hemorrhages, longitudinal ulcerations, rapid resolution on serial examinations 1
- Colonoscopy establishes diagnosis in >90% of cases but may be risky in acute setting; sigmoidoscopy with abdominal CT is safer alternative 1
- Age consideration: Lower threshold for suspicion in elderly patients (≥65 years) who have higher hospitalization and mortality rates 2
C. difficile-Associated Diarrhea (CDAD):
- Risk factors: Recent antibiotic use (within 2 months), IBD patients, immunosuppression, corticosteroid use 1, 6
- Clinical presentation: Can range from mild diarrhea to fatal colitis; pseudomembranes may be absent in IBD patients 1, 6
- Testing: Stool PCR or toxin assay; blood cultures if febrile or toxic-appearing 2
Conditions with Overlapping Symptoms
Irritable Bowel Syndrome (IBS):
- Post-infectious IBS develops in 4-26% of patients after acute gastroenteritis, accounting for >50% of all IBS cases 4, 7
- Faecal calprotectin <100 μg/g with appropriate clinical context suggests IBS rather than IBD 1, 8
- Low-grade inflammation may persist after acute infection, detectable via faecal calprotectin and intestinal biopsies 7
- Prognosis: No evidence that post-infectious IBS carries better prognosis than IBS generally 7
Food Protein-Induced Enterocolitis Syndrome (FPIES):
- Primarily infantile disorder with symptoms overlapping chronic gastroenteritis 1
- Clinical features: Acute onset vomiting 1-4 hours after trigger food, lethargy, pallor, potential hypovolemic shock (15% of cases) 1
- Diagnostic approach: Do not use stool tests for diagnosis; consider workup to rule out other GI diseases with overlapping symptoms 1
- Histology: Red, fragile, hemorrhagic mucosa with severe inflammation and increased eosinophils on biopsy 1
Microscopic Colitis:
- Consider when: Persistent watery diarrhea without blood, normal colonoscopy appearance, symptoms not improving with standard gastroenteritis treatment 1
- Diagnosis requires: Colonic biopsies showing lymphocytic or collagenous colitis 1
Bile Acid Malabsorption:
- Clinical clue: Chronic watery diarrhea persisting after acute gastroenteritis resolves 1
- Consider in: Patients with terminal ileal disease or resection, post-cholecystectomy 1
Diagnostic Algorithm
For patients aged 16-40 with new lower GI symptoms >4 weeks where IBD suspected: 1
- Obtain in primary care: Full blood count, urea & electrolytes, CRP, coeliac screen, stool culture 1
- Check faecal calprotectin (not appropriate if NSAID use in past 6 weeks) 1
- Interpret results:
- <100 μg/g: Treat as IBS in primary care; consider other diagnoses if symptoms persist (bile acid malabsorption, microscopic colitis, medication effects) 1
- 100-250 μg/g: Repeat testing or routine gastroenterology referral based on clinical suspicion 1
250 μg/g: Urgent gastroenterology referral for colonoscopy 1
For acute presentation with bloody diarrhea: 1
- Flexible sigmoidoscopy with biopsy from at least one site to differentiate UC from other causes of acute colitis 1
- Stool studies: Multiplex antimicrobial testing, C. difficile if recent antibiotics, blood cultures if febrile 1, 2, 4
- Avoid colonoscopy and bowel purgatives in acute severe colitis due to perforation risk 1
For suspected intra-abdominal complications: 1
- Cross-sectional imaging (CT, MRI, ultrasound) to detect strictures, fistulae, and abscesses 1
- Contrast-enhanced CT is key study in emergency setting 1
Common Pitfalls to Avoid
- Do not delay rehydration while awaiting diagnostic testing; initiate ORS or IV fluids immediately based on dehydration severity 2
- Do not rely solely on CRP/ESR to rule out IBD activity, especially with proximal/ileal disease where false negatives occur 1
- Do not perform colonoscopy in acute severe colitis; flexible sigmoidoscopy is sufficient and safer 1
- Do not assume negative stool culture excludes infection; cultures are positive in only 40-60% of infectious colitis cases 1
- Do not underestimate dehydration in elderly patients who may not manifest classic signs and have higher mortality risk 2
- Do not use antimotility agents (loperamide) in children <18 years or in bloody diarrhea due to risk of toxic megacolon and serious adverse events 2, 9