Evaluation of Chronic Diarrhea GREGORY JUCKETT, MD, MPH, and RUPAL TRIVEDI, MD West Virginia University, Morgantown, West Virginia
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Evaluation of Chronic Diarrhea GREGORY JUCKETT, MD, MPH, and RUPAL TRIVEDI, MD West Virginia University, Morgantown, West Virginia Chronic diarrhea, defined as a decrease in stool consistency for more than four weeks, is a common but challeng- ing clinical scenario. It can be divided into three basic categories: watery, fatty (malabsorption), and inflammatory. Watery diarrhea may be subdivided into osmotic, secretory, and functional types. Watery diarrhea includes irritable bowel syndrome, which is the most common cause of functional diarrhea. Another example of watery diarrhea is microscopic colitis, which is a secretory diarrhea affecting older persons. Laxative-induced diarrhea is often osmotic. Malabsorptive diarrhea is characterized by excess gas, steatorrhea, or weight loss; giardiasis is a classic infectious example. Celiac disease (gluten-sensitive enteropathy) is also malabsorptive, and typically results in weight loss and iron deficiency anemia. Inflammatory diarrhea, such as ulcerative colitis or Crohn disease, is characterized by blood and pus in the stool and an elevated fecal calprotectin level. Invasive bacteria and parasites also produce inflamma- tion. Infections caused by Clostridium difficile subsequent to antibiotic use have become increasingly common and virulent. Not all chronic diarrhea is strictly watery, malabsorptive, or inflammatory, because some categories over- lap. Still, the most practical diagnostic approach is to attempt to categorize the diarrhea by type before testing and treating. This narrows the list of diagnostic possibilities and reduces unnecessary testing. Empiric therapy is justi- fied when a specific diagnosis is strongly suspected and follow-up is available.Am ( Fam Physician. 2011;84(10):1119- 1126. Copyright © 2011 American Academy of Family Physicians.) ▲ Patient information: hronic diarrhea is defined as a continue despite fasting and occur at night. A handout on chronic decrease in stool consistency con- Stimulant laxatives fall into this secretory diarrhea, written by the 1 3 authors of this article, is tinuing for more than four weeks. category because they increase motility. Per- provided on page 1133. Although reasonably common sons with functional disorders have smaller C (3 to 5 percent of the population), it repre- stool volumes (less than 350 mL per day) and sents a considerable diagnostic challenge, no diarrhea at night.3 with several hundred conditions in the dif- ferential diagnosis.1 This article focuses on a Medical History diagnostic approach that is practical for the A history is the critical first step in diagnosis. primary care physician. It is important to understand exactly what patients mean when they say they have diar- Categorization rhea. A patient may not actually have diar- Chronic diarrhea may be divided into three rhea, but incontinence occasioned by fecal basic categories: watery, fatty (malabsorp- impaction.4 Stool volume, frequency, and tion), and inflammatory (with blood and consistency can help categorize the diarrhea, pus). However, not all chronic diarrhea is as previously mentioned. A travel history is strictly watery, malabsorptive, or inflamma- essential. Travel to the tropics vastly expands tory, because some categories overlap. The the list of diagnostic possibilities, but in no differential diagnosis of chronic diarrhea is way rules out common causes. Bloody diar- described in Table 1.1,2 rhea after a trip to Africa may still be ulcer- Watery diarrhea may be subdivided into ative colitis rather than amebic dysentery. osmotic (water retention due to poorly absorbed substances), secretory (reduced Physical Examination water absorption), and functional (hyper- Physical examination provides additional motility) types.1 Osmotic laxatives, such as clues to the cause of diarrhea. Recent weight sorbitol, induce osmotic diarrhea. Secretory loss or lymphadenopathy could result from diarrhea can be distinguished from osmotic chronic infection or malignancy. Eye find- and functional diarrhea by virtue of higher ings, such as episcleritis or exophthalmia, stool volumes (greater than 1 L per day) that suggest that the diarrhea is attributable to Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright © 2011 American Academy of Family Physicians. For the private, noncommercial November use15, of2011 one individual◆ Volume user 84, of Numberthe Web site. 10 All other rights reserved.www.aafp.org/afp Contact [email protected] for copyright questionsAmerican and/or permissionFamily Physician requests. 1119 Chronic Diarrhea SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence Clinical recommendation rating References Chronic diarrhea should be categorized as watery (secretory vs. osmotic vs. functional), fatty, C 1 or inflammatory before full diagnostic evaluation. The fecal osmotic gap can help distinguish secretory from osmotic diarrhea. C 1 Most persons with irritable bowel syndrome meeting Rome III criteria do not require colonoscopy C 15 if the condition responds to therapy. Fecal calprotectin, a marker for neutrophil activity, is useful for distinguishing inflammatory bowel C 17, 18 disease from irritable bowel syndrome and for monitoring inflammatory bowel disease activity. Testing for celiac disease should be considered in patients with irritable bowel syndrome, type 1 C 6 diabetes mellitus, thyroid disease, iron deficiency anemia, weight loss, infertility, elevated liver transaminase levels, and chronic fatigue. A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease- oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp. org/afpsort.xml. Table 1. Differential Diagnosis of Chronic Diarrhea Watery Fatty (bloating and steatorrhea in Inflammatory or exudative Secretory (often nocturnal; unrelated to food many, but not all cases) (elevated white blood intake; fecal osmotic gap < 50 mOsm per kg*) Malabsorption syndrome (damage to or cell count, occult or frank Alcoholism loss of absorptive ability) blood or pus) Bacterial enterotoxins (e.g., cholera) Amyloidosis Inflammatory bowel disease Bile acid malabsorption Carbohydrate malabsorption (e.g., lactose Crohn disease (ileal or early Crohn disease may be Brainerd diarrhea (epidemic secretory diarrhea) intolerance) secretory) Congenital syndromes Celiac sprue (gluten enteropathy)–various clinical presentations Diverticulitis Crohn disease (early ileocolitis) Gastric bypass Ulcerative colitis Endocrine disorders (e.g., hyperthyroidism Ulcerative jejunoileitis [increases motility]) Lymphatic damage (e.g., congestive heart failure, some lymphomas) Invasive infectious diseases Medications (see Table 3) Medications (e.g., orlistat [Xenical; inhibits Clostridium difficile Microscopic colitis (lymphocytic and collagenous fat absorption], acarbose [Precose; (pseudomembranous) subtypes) inhibits carbohydrate absorption]) colitis–antibiotic history Neuroendocrine tumors (e.g., gastrinoma, Mesenteric ischemia Invasive bacterial infections vipoma, carcinoid tumors, mastocytosis) Noninvasive small bowel parasite (e.g., tuberculosis, Nonosmotic laxatives (e.g., senna, docusate (e.g., Giardia) yersiniosis) sodium [Colace]) Postresection diarrhea Invasive parasitic infections Postsurgical (e.g., cholecystectomy, gastrectomy, Short bowel syndrome (e.g., Entamoeba)–travel vagotomy, intestinal resection) history Vasculitis Small bowel bacterial overgrowth (> 105 bacteria per mL) Ulcerating viral infections Osmotic (fecal osmotic gap > 125 mOsm per kg*) (e.g., cytomegalovirus, Tropical sprue Carbohydrate malabsorption syndromes herpes simplex virus) Whipple disease (Tropheryma whippelii (e.g., lactose, fructose) Neoplasia infection) Celiac disease Colon carcinoma Maldigestion (loss of digestive function) Osmotic laxatives and antacids Lymphoma Hepatobiliary disorders (e.g., magnesium, phosphate, sulfate) Villous adenocarcinoma Inadequate luminal bile acid Sugar alcohols (e.g., mannitol, sorbitol, xylitol) Radiation colitis Functional (distinguished from secretory Loss of regulated gastric emptying types by hypermotility, smaller volumes, and Pancreatic exocrine insufficiency improvement at night and with fasting) Irritable bowel syndrome *—Fecal osmotic gap = 290 – 2 × (stool sodium + stool potassium). It helps differentiate secretory from osmotic diarrhea. Normal fecal osmolality is 290 mOsm per kg (290 mmol per kg). Although measurement of fecal electrolytes is no longer routine, knowing the fecal osmotic gap helps confirm whether watery stools represent chronic osmotic diarrhea (fecal osmotic gap greater than 125 mOsm per kg [125 mmol per kg]) or chronic secretory diarrhea (fecal osmotic gap less than 50 mOsm per kg [50 mmol per kg]).1 Information from references 1 and 2. 1120 American Family Physician www.aafp.org/afp Volume 84, Number 10 ◆ November 15, 2011 Chronic Diarrhea inflammatory bowel disease (IBD) and hyperthyroid- of diarrhea, 24-hour stool collection can quantify stool ism, respectively. Dermatitis herpetiformis, an itchy production. blistering rash, is found in 15 to 25 percent of patients with celiac disease.5 An abdominal examination for scars Diagnostic Approach (surgical causes of diarrhea), bowel sounds (hypermo- It is usually impractical to test and treat the many pos- tility), tenderness (infection and inflammation), and sible causes of chronic diarrhea. In most cases, it is more masses (neoplasia)