Chronic Diarrhea of Unknown Origin

What is Chronic Diarrhea of Unknown Origin?

Chronic diarrhea is the frequent passage of loose, watery stools that persists for more than four weeks. When a comprehensive medical evaluation—including a detailed history, physical exam, blood tests, stool analysis, and endoscopic procedures—fails to identify a specific cause, the condition is referred to as chronic diarrhea of unknown origin. This can be a frustrating situation for both patients and physicians, as it represents a diagnostic challenge where the root cause of the symptoms remains hidden despite an extensive investigation. It is a diagnosis of exclusion, established only after all other known causes have been systematically ruled out.

What are the symptoms?

The primary symptom is persistent, often watery, non-bloody diarrhea lasting for more than four weeks. The frequency and volume of bowel movements can vary significantly. Other associated symptoms may include:

• Abdominal cramping or pain
• Bloating and excess gas
• Urgency to have a bowel movement
• Fecal incontinence or soiling
• Nausea or loss of appetite
• Fatigue

What are the potential causes?

When the cause of chronic diarrhea remains elusive after a standard workup, it often falls into one of several categories that may require more specialized testing to diagnose.

• Functional Bowel Disorders: Irritable Bowel Syndrome with Diarrhea (IBS-D) is one of the most common causes. It is a disorder of the gut-brain axis, leading to diarrhea and abdominal pain without any visible inflammation or damage.
• Microscopic Colitis: This is an inflammatory condition of the colon that is only visible when biopsies are examined under a microscope. The colon lining appears normal during colonoscopy. The two types are lymphocytic colitis and collagenous colitis.
• Bile Acid Malabsorption (BAM): Sometimes, bile acids are not properly reabsorbed in the small intestine. When they reach the colon, they can irritate the lining and cause a watery, urgent diarrhea.
• Medication Side Effects: A thorough review of all medications is crucial, as many drugs, including some antibiotics, metformin, and even over-the-counter NSAIDs, can cause chronic diarrhea.
• Dietary Factors: Undiagnosed intolerances to substances like lactose, fructose, gluten (in non-celiac gluten sensitivity), or artificial sweeteners can lead to persistent diarrhea.
• Small Intestinal Bacterial Overgrowth (SIBO): An excessive amount of bacteria in the small intestine can interfere with digestion and lead to diarrhea, gas, and bloating.

How is the cause of chronic diarrhea diagnosed?

The evaluation for chronic diarrhea is a stepwise process designed to systematically rule out potential causes.

• Initial Workup: The investigation begins with a detailed history, physical exam, and initial laboratory tests, including a complete blood count, inflammatory markers (CRP), thyroid function tests, and blood tests for celiac disease.
• Stool Studies: Stool samples are analyzed to rule out infections from bacteria, viruses, and parasites. A fecal calprotectin test is also useful, as a high level points towards an inflammatory cause like IBD, while a normal level suggests a functional or non-inflammatory cause.
• Colonoscopy with Biopsies: A colonoscopy is essential in the workup of chronic diarrhea. It allows for direct visualization of the colon lining to look for signs of IBD or tumors. Crucially, biopsies must be taken from multiple segments of the colon, even if it looks normal, to rule out microscopic colitis.
• Further Testing: If the above tests are unrevealing, more specialized tests may be performed, such as breath tests for SIBO or lactose intolerance, stool tests for bile acid malabsorption, or imaging of the small intestine with a CT or MR enterography.

How is chronic diarrhea of unknown origin treated?

Treatment is ideally directed at the underlying cause once it is found. While the diagnostic workup is ongoing, or if a definitive cause cannot be identified, treatment is focused on managing the symptoms.

• Dietary Modifications: Keeping a food diary can help identify trigger foods. Often, a trial of avoiding common irritants like caffeine, alcohol, artificial sweeteners, and high-fat foods is helpful. A low-FODMAP diet can be effective for many people with functional diarrhea.
• Bulking Agents: Soluble fiber supplements (like psyllium or methylcellulose) can help absorb excess water in the colon and add form to the stool.
• Anti-diarrheal Medications: Medications like loperamide are effective for reducing the frequency and urgency of bowel movements. For suspected bile acid malabsorption, a trial of a bile acid binder like cholestyramine may be both diagnostic and therapeutic.
• Probiotics: While evidence is mixed, some people find that probiotics help to regulate their bowel function.

If all my tests are normal, does that mean my diarrhea is caused by stress?
If a comprehensive medical workup is negative, a diagnosis of a functional bowel disorder like Irritable Bowel Syndrome with Diarrhea (IBS-D) is often made. While stress does not cause these disorders, it is a well-known factor that can trigger or significantly worsen the symptoms through the complex gut-brain connection.

Could my chronic diarrhea be cancer?
While it is a common concern, colorectal cancer is an infrequent cause of chronic watery diarrhea, especially without other alarm symptoms like bleeding or weight loss. A colonoscopy is a key part of the evaluation to definitively rule out cancer and pre-cancerous polyps.

• Schiller LR, Pardi DS, Sellin JH. Chronic Diarrhea: Diagnosis and Management. Clin Gastroenterol Hepatol. 2017;15(2):182-193.e3.
• National Institute of Diabetes and Digestive and Kidney Diseases. Diarrhea. Published May 2016. Accessed October 14, 2025. https://www.niddk.nih.gov/health-information/digestive-diseases/diarrhea
• Lacy BE, Mearin F, Chang L, et al. Bowel Disorders. Gastroenterology. 2016;150:1393-1407.