Diarrhea, Malabsorption & Celiac
Sorting acute from chronic, osmotic from secretory, and celiac from IBS
Acute diarrhea and when to intervene
Mostly viral, mostly self-limited. Acute diarrhea lasts under 14 days (14–30 days is persistent; beyond 30 days, chronic). Most cases are viral, with norovirus the most common cause, and resolve on their own. Oral rehydration solution, not antibiotics, is the cornerstone; most patients need neither stool studies nor antimicrobials.
When to test and treat. Send stool studies (culture or multiplex PCR, Shiga toxin testing) and consider antibiotics when there is:
- Dysentery: bloody stool with fever
- Severe dehydration or need for hospitalization
- Immunocompromise
- Symptoms lasting more than 7 days
The EHEC exception. Enterohemorrhagic E. coli O157:H7, classically from undercooked ground beef, causes bloody diarrhea, often with little fever. Antibiotics and antimotility agents raise the risk of hemolytic uremic syndrome (microangiopathic hemolytic anemia, thrombocytopenia, and AKI) by increasing Shiga toxin release and exposure. Management is supportive: hydration and monitoring of blood counts and creatinine.
A child with bloody diarrhea after a hamburger gets fluids, not antibiotics or loperamide.
Clostridioides difficile
Pathogenesis. Antibiotics (classically clindamycin, fluoroquinolones, and cephalosporins) and PPIs disrupt the colonic flora, allowing C. difficile to overgrow. Its toxins A and B cause watery diarrhea and pseudomembranous colitis.
Diagnosis. Test unformed stool from a patient with 3 or more loose stools in 24 hours who is not taking laxatives, using NAAT and/or toxin EIA. Do not test formed stool or test for cure. Severe disease: WBC ≥15,000/μL or creatinine >1.5 mg/dL. Fulminant disease: hypotension, ileus, or megacolon.
Treatment. Stop the offending antibiotic when possible. First-line therapy is now oral vancomycin or fidaxomicin; metronidazole is no longer preferred. Fulminant disease adds IV metronidazole to high-dose oral vancomycin, with surgical consultation for megacolon or perforation. Recurrence is treated with fidaxomicin, and repeated recurrences with fecal microbiota transplant. Soap-and-water handwashing matters because alcohol gel does not kill spores.
IV vancomycin does not treat C. difficile: it is not secreted into the colon lumen, so it must be given orally.
Classifying chronic diarrhea
Stool osmotic gap = 290 − 2 × (stool Na + K). A high gap means unmeasured osmoles in the stool; a low gap means the stool water is driven by secreted electrolytes. The best bedside discriminator is fasting: osmotic diarrhea stops, secretory diarrhea does not.
| Type | Clues | Examples |
|---|---|---|
| Osmotic | Gap >125; stops with fasting | Lactase deficiency, laxatives, magnesium |
| Secretory | Gap <50; persists with fasting; large volume, often nocturnal | Cholera toxin, VIPoma, carcinoid, bile acid diarrhea |
| Inflammatory | Blood and mucus, fever; raised fecal calprotectin, lactoferrin, or leukocytes | IBD, radiation colitis, chronic infection (Entamoeba histolytica, C. difficile, CMV) |
| Fatty (malabsorptive) | Greasy, foul, floating stools; weight loss; excess fecal fat | Celiac disease, pancreatic insufficiency, SIBO |
Lactose intolerance is the most common osmotic cause: bloating and diarrhea after dairy, a positive hydrogen breath test, and relief with avoidance or lactase supplements. For steatorrhea, the D-xylose test separates mucosal disease (low absorption, as in celiac disease) from pancreatic insufficiency (normal absorption).
Celiac disease
Presentation. An immune reaction to gluten in HLA-DQ2/DQ8 carriers damages the proximal small bowel. Look for chronic diarrhea, bloating, weight loss, iron-deficiency anemia that fails oral iron, osteoporosis, or unexplained transaminase elevation. Celiac disease clusters with type 1 diabetes, autoimmune thyroid disease, Down syndrome, and selective IgA deficiency.
- Eating glutenRequired for testing; a gluten-free diet causes false-negative serology and biopsy.
- tTG-IgA plus total IgAFirst-line serologic screen; selective IgA deficiency gives false negatives, so use IgG-based tests if IgA is low.
- Duodenal biopsyVillous atrophy, crypt hyperplasia, intraepithelial lymphocytosis: the confirmatory test.
- Gluten-free dietConfirms and treats; falling tTG titers show adherence and mucosal healing.
HLA typing. HLA-DQ2/DQ8 has a high negative predictive value; its absence essentially excludes celiac disease, which helps when a patient is already avoiding gluten.
Dermatitis herpetiformis. The skin manifestation: intensely pruritic grouped vesicles on the extensor surfaces with granular IgA deposits at the dermal papillae. It responds to a gluten-free diet and to dapsone.
Treatment and complications. A lifelong gluten-free diet: no wheat, barley, or rye (pure oats are usually tolerated). Persistent symptoms usually mean ongoing gluten exposure. Watch for iron-deficiency anemia, osteoporosis, and enteropathy-associated T-cell lymphoma.
IBS, microscopic colitis, and SIBO
IBS (Rome IV). Recurrent abdominal pain at least 1 day per week over the last 3 months, associated with two or more of: relation to defecation, a change in stool frequency, or a change in stool form. There must be no alarm features: weight loss, bleeding, anemia, nocturnal symptoms, or onset after age 50. Subtypes are IBS-C, IBS-D, and IBS-M. A limited workup suffices (CBC; celiac serology and fecal calprotectin or CRP when diarrhea predominates). Management starts with education, a low-FODMAP diet, and soluble fiber.
| Target | Drugs | Notes |
|---|---|---|
| IBS-C | Polyethylene glycol, linaclotide, lubiprostone | Linaclotide is a guanylate cyclase-C agonist; lubiprostone opens chloride channels |
| IBS-D | Loperamide, rifaximin, eluxadoline | Eluxadoline is avoided after cholecystectomy (pancreatitis risk) |
| Pain-predominant | Antispasmodics (dicyclomine), low-dose TCAs | TCAs also slow transit, suiting IBS-D |
Microscopic colitis. Chronic watery, nonbloody diarrhea, typically in older women, with a normal-appearing colonoscopy; only biopsy shows collagenous colitis (thick subepithelial collagen band) or lymphocytic colitis (intraepithelial lymphocytes). It is linked to NSAIDs, PPIs, and SSRIs. Stop the offending drug; budesonide is first-line.
Small intestinal bacterial overgrowth. Bloating, diarrhea, and fat malabsorption with the classic pattern of low vitamin B12 and high folate: bacteria consume B12 but synthesize folate, so macrocytic anemia can result. Risk factors are strictures, diabetic or scleroderma dysmotility, and blind loops after surgery. Diagnose with a hydrogen breath test and treat with rifaximin.