In the United States, acute diarrhea is the second most commonly reported illness after respiratory infections, and worldwide, diarrhea is the leading cause of death in children less than four years of age. Diarrhea is best defined as an abnormal looseness of the stool, and may include changes in stool frequency, consistency, urgency and continence, often with the related symptoms of cramping and bloating. The symptom of diarrhea, however, is to a large extent subjective; people define it based on their own experience. Diarrhea becomes a problem when the change in bowel habits becomes annoying or distressing to the individual, or when it is associated with or causes a change in the person's well being. Acute Diarrhea
Acute diarrhea is defined as the passage of a greater number of stools of looser form than is customary, with a duration lasting no longer than 2 weeks, often with discomfort from associated gas, cramping and bloating. Severity of diarrhea may be defined as mild (no changes in activities required by the patient), moderate (change in activities required but the person is able to function), or severe (patient is disabled, often confined to bed or room). The incidence of acute diarrhea in the United States is approximately one episode per person per year, making it one of the most common medical disorders seen by primary care practitioners.

Patients with intense diarrhea and large fluid and electrolyte losses may develop dehydration that will need medical evaluation. Dehydrating illness is particularly problematic for the very young or very old. No firm conclusions can be drawn from the symptoms or the severity of the illness as to its likely cause.

The volume of the diarrhea may help to localize the disease process within the GI tract. Frequent, small volume bowel movements typically are associated with diseases of the left colon or rectum, and watery large volume movements suggest disorders of the small bowel or proximal colon. Urgency and cramping typically indicates inflammation in the rectum. Nocturnal diarrhea may be seen in infectious colitis or severe inflammatory bowel disease, and is not a feature of irritable bowel syndrome.

It is important to investigate medication use; acute diarrhea is a common side effect of a new medicine or one which contains magnesium. Antibiotic associated diarrhea is frequent, whether as a result of the medication itself or secondary to the production of a toxin by Clostridium difficile. Use of alcohol or illicit drugs (particularly methamphetamine) should be ascertained. The intake of coffee, tea or colas may lead to caffeine or methylxanthine induced diarrhea. Dietetic foods, gums or mints may contain poorly absorbed sugars such as sorbitol or mannitol which cause osmotic diarrhea.

Traveler's diarrhea, usually caused by enterotoxic Escherichia coli, is common, particularly in travelers to developing portions of the world, such as Mexico, the Mid East and India. Some more unusual infections are suggested by the site of the recent travel. For example, camping in the mountains (and drinking untreated water) raises concern for Giardia lamblia infection. With increased international and adventure travel have come more exotic pathogens that need to be considered. Infection with Cyclospora cayetanensis and Cryptosporidium parvum from travel to Nepal and St. Petersburg (Leningrad), respectively, are illustrative. Living in proximity to farm animals, or visiting petting zoos may lead to exposure to Salmonella, Brucella, or Cryptosporidia. Eating contaminated foods such as ground beef may expose a person to Escherichia coli 0157:H7, a cause of bloody diarrhea. Campylobacter infection may result from eating undercooked chicken or turkey. Health care workers are at increased risk for nosocomial infections (e.g., Clostridium difficile). Sexual practices may yield clues as to the etiology of diarrhea. Anal intercourse is a risk factor for proctitis, caused by Entamoeba histolytica, Treponema pallidum (syphilis), Neisseria gonorrhea, Chlamydia, and Herpes simplex in addition to more common bacterial pathogens. With the AIDS pandemic, one needs to be alert for opportunistic infections that may present as acute diarrheal illness.

A distended, rigid or tender abdomen may indicate a potential catastrophe, and prompt immediate, aggressive evaluation for its cause. Most episodes of acute diarrhea are managed by the affected person or by a family member with dietary modifications or with the use of available OTC medications. These can assist in reducing frequency of stools while others address symptoms of gas or bloating and newer combined formulations can do both.

In patients with mild, acute diarrhea, no immediate laboratory evaluation is needed as the results often will become available only after symptoms have subsided. Laboratory evaluation should be restricted to patients with severe diarrhea or when illness is complicated by the presence of dysentery, fever, or when the duration of illness becomes protracted. Stool cultures are not routinely indicated. They should be performed in patients with severe diarrhea and fever, dysentery, fecal leukocytes, or a prolonged (greater than 14 days) diarrheal illness.

Examination of stool for ova and parasites is indicated in patients with prolonged diarrhea, or who have particular circumstances (e.g., travel, occupation, immunocompromised status) that make them susceptible to parasitic infestation. When parasites are suspected, obtaining three fresh stool samples for immediate examination will provide better results than just one.

Conventional Treatment of Acute Diarrhea
Fluid repletion is important even for the majority of patients who have mild diarrhea. Oral replacement solutions should be used. The World Health Organization solution as well as commercially available preparations can be given both for rehydration and maintenance fluid requirements. These solutions are preferable to dilute fruit juices, uncarbonated soft drinks, or tea with sugar. Dietary modifications also may be helpful to the patient with mild, acute diarrhea. Milk and dairy products should be withheld for 24 to 48 hours, and initial refeeding may begin with cereals, starches, soups and broth.

Therapy with antidiarrheal medications is indicated for relief of the debilitating symptoms that accompany many diarrheal illnesses. Most patients can take antidiarrheal medications safely to improve their symptoms, although care must be taken not to administer antimotility agents to patients in whom a toxin producing or invasive bacteria is suspected.

Attapulgite binds water, as a result of which the stools are more formed. Attapulgite and kaolin are believed to work also by adsorbing the causative agent (bacteria or germ) and removing it from the body. It is recognized as one of the safer antidiarrheal therapies, as it exerts its effect only within the bowel lumen. Another agent, bismuth subsalicylate exerts its effect both through its antisecretory salicylate moiety and possibly also by its antimicrobial activity; it improves the symptoms of nausea and vomiting that are associated with gastroenteritis. Since bismuth subsalicylate contains non aspirin salicylate, care must be taken when it is used in patients taking medication for anticoagulation, diabetes and gout.

Most of the commonly employed antidiarrheal medications are antimotility agents that act by slowing intestinal motility, thereby increasing intraluminal fluid time and allowing for greater intestinal fluid absorption. One of the most widely used and best tolerated of these medications is loperamide. Caution must be taken when considering administration of an antimotility antidiarrheal agent in a patient with high fever or dysentery, as these medications may lead to a worsening of infectious diarrhea due to bowel stasis and increased bowel wall penetration by invasive pathogens (e.g., Shigella). The use of agents such as loperamide in acute diarrhea, and particularly in traveler's diarrhea, is usually safe in the absence of bloody diarrhea or high fever. Patients with diarrhea often have associated symptoms of nausea and bloating, and combination therapy with loperamide and simethicone is now available. Novel antisecretory compounds, which improve diarrhea through more physiologic mechanisms than do currently available agents, are in development and may become an important part of therapy in the future.

Patients in whom the use of antibiotics may be useful include those who have criteria of severe illness: high fever, signs of systemic toxicity, dysentery, or moderate to severe "traveler's diarrhea." In general, the drug of choice is a fluoroquinolone, given for one to three days. Specific therapy may be directed if stool cultures or other studies reveal a particular pathogen.

When diarrhea is more intense (for example, passage of more than 6 unformed stools per 24 hours, or associated with blood) or lasts longer than 48 hours, medical evaluation and treatment should be sought.

Chronic Diarrhea
Chronic diarrhea, especially if associated with abdominal pain or systemic symptoms, can limit activity, adversely influence quality of life, and pose diagnostic and management challenges to health care providers. Chronic diarrhea is defined as an increased stool frequency and fluidity (looseness) lasting more than two weeks. It should be distinguished from other conditions such as incontinence, which is involuntary defecation. Careful history and physical examination can determine the likely cause of most chronic diarrhea and direct subsequent diagnostic evaluation and treatment. One approach to the problem is to determine whether diarrheal stools are bloody, fatty or watery.

The most likely cause of chronic bloody diarrhea is inflammatory bowel disease (IBD), i.e. ulcerative colitis or Crohn's disease. Symptoms of tenesmus or incomplete evacuation suggest rectal inflammation. A palpable abdominal mass or tenderness, perianal fistulae, oral aphthous ulcers, sacroiliac, spinal or peripheral arthropathy, or skin changes (erythema nodosum or pyoderma gangrenosum) all suggest a diagnosis of IBD.

Less common causes of chronic bloody diarrhea include ischemia, infections (Campylobacter jejuni, Clostridium difficile, Entamoeba histolytica, Yersinia, and Cytomegalovirus), radiation or chemotherapy, and colon cancer or polyps (villous adenoma).

Maldigestion or malabsorption of fat can lead to chronic diarrhea. Fatty stools typically are bulky, greasy, and particularly malodorous. They may float because of excess gas content resulting from bacterial fermentation of unabsorbed dietary material. Individuals with maldigestion often are not systemically ill and can maintain their weight and activity in spite of massive steatorrhea because of a voracious appetite. The most frequent cause of maldigestion is pancreatic insufficiency caused by chronic pancreatitis. Those with suspected maldigestion should be asked about alcohol abuse, the most common cause of chronic pancreatitis in the United States. Severe or recurrent abdominal pain, profound weight loss, abdominal trauma or a positive family history may suggest less common causes of pancreatic insufficiency such as traumatic or hereditary pancreatitis, cystic fibrosis, congenital structural pancreatic abnormalities (pancreas divisum) or pancreatic cancer. Bile salt deficiency due to biliary tract obstruction, cholestatic liver disease, bacterial overgrowth or excessive stool losses (IBD, terminal ileal resection) also can lead to maldigestion but usually this is not associated with significant steatorrhea.

Small bowel mucosal disease or surgical resection can lead to malabsorption of fats as well as carbohydrates, proteins, vitamins and minerals, all of which can result in weight loss and various systemic signs and symptoms. Gluten sensitive enteropathy (celiac sprue) is the most common mucosal cause of malabsorption in the United States. Individuals with sprue are likely to have a positive family history, history of diabetes or skin lesions (dermatitis herpetiformis) and have manifestations of panmalabsorption dating back to childhood or adolescence. Short stature, weakness due to multifactorial anemia (iron, folate and occasional vitamin B12 deficiency), bone pain and spontaneous fractures from vitamin D and calcium malabsorption, bruising and bleeding related to vitamin K deficiency, gas and bloating due to carbohydrate malabsorption, and edema from albumin and protein loss are typical complaints of those with sprue and other small bowel mucosal diseases. Whipple's disease, tropical sprue, and Zollinger Ellison syndrome are less common mucosal conditions leading to malabsorption.

Many disorders can cause chronic watery diarrhea including carbohydrate malabsorption (lactose intolerance, sorbitol, fructose), intestinal infections or inflammation, unusual hormone secreting tumors, and irritable bowel syndrome. Careful medication history is important since such medications as NSAIDs, antacids, elixirs (containing sorbitol and fructose), antihypertensives, cholinergic agents, antibiotics, and antiarrhythmics all can cause diarrhea in some individuals. Most commonly, carbohydrate malabsorption induces an osmotic diarrhea accompanied by abdominal bloating and flatulence that is associated with meals. Such osmotic diarrhea typically abates during periods of fasting. Lactase deficiency, either ethnically acquired (more common in Asian Americans, African Americans) or secondary to acute infectious enteritis can lead to diarrhea following ingestion of milk, cheese, ice cream and other dairy products. Less commonly recognized causes of diarrhea due to carbohydrate malabsorption include ingestion of sorbitol and fructose found in certain soft drinks, juices, dried fruits, and sugar free gum or candy. A history of any relation of diarrhea to foods is important to obtain, particularly in children who seem to be more sensitive to ingested sorbitol and fructose and in older adults who may have chronic mesenteric ischemia.

Giardiasis can produce chronic symptoms, as can some opportunistic infections (e.g., microsporidiosis, cryptosporidiosis, infection with MAI or CMV) in immune suppressed individuals. Epidemics of chronic diarrhea have occurred following ingestion of unpasteurized milk but no infectious agent has been isolated in such cases. In some individuals, diarrhea may persist for months following apparent acute infectious enteritis, presumably due to secondary carbohydrate malabsorption or dysmotility from intestinal neuromuscular injury. An unusual condition, microscopic colitis, can cause chronic persistent watery diarrhea in middle aged or older individuals. While the etiology of microscopic colitis is unknown, it has been linked to gluten sensitive enteropathy, diabetes, and NSAID use, and can, in some individuals, cause nocturnal fecal incontinence.

Diabetes presumably causes chronic watery diarrhea as a result of intestinal neuropathy, bacterial overgrowth, or both. Diabetic diarrhea can occur at night, be interspersed with periods of constipation, and be associated with fecal incontinence. Individuals with diabetic diarrhea usually have severe long standing glucose intolerance associated with other diabetic complications such as retinopathy, nephropathy, and neuropathy.

Several unusual hormone producing neoplasms can cause watery diarrhea. These include carcinoid tumors and tumors producing vasoactive intestinal polypeptide and glucagon. Large volume and frequent watery stools that persist during fasting and that are associated with severe fluid and electrolyte abnormalities and dehydration characterize these endocrine neoplasms. Family history of multiple endocrine neoplastic syndrome; a history of severe ulcer disease (Zollinger Ellison syndrome); episodic hypotension, vasomotor flushing, or valvular cardiac disease (carcinoid syndrome); or the presence of a scaling, erythematous dermatitis (necrolytic migratory erythema in a patient with a glucagonoma) may offer clues to the diagnosis.

Irritable bowel syndrome (IBS) is the reason patients most commonly seek attention for chronic watery diarrhea. It is important to distinguish IBS from other conditions that cause chronic diarrhea, since in most persons with IBS, the problem is frequent defecation rather than voluminous diarrhea. Abdominal pain is the key symptom of IBS, and frequent stools often contain mucus and are accompanied by or preceded by abdominal cramps, and abdominal pain is the key symptom of IBS. Periods of loose stools can be interspersed with periods of constipation. IBS symptoms may worsen during times of emotional or physiologic stress. Those with especially severe symptoms and persistent lower abdominal pain may have been physically or sexually abused in the past. While a diagnosis of "non disease" is often difficult to make, irritable bowel syndrome is thought to be a functional disorder (dysmotility) since no anatomic or organic intestinal problems are found to explain the symptoms.

Laboratory Testing
The purposes of basic laboratory tests are: a) to assess the impact of chronic diarrhea on the patient's overall nutritional and electrolyte status, and b) to form a preliminary judgment about the characteristics of the diarrhea. A complete blood count should be obtained to look for evidence of anemia or an abnormal white blood cell count. Biochemical screening should include serum electrolytes, tests of renal function (blood urea nitrogen and creatinine) and a basic nutritional assessment, consisting of a lymphocyte count and measurements of serum calcium, phosphorus, total protein and albumin levels.

The type of diarrhea can be defined by evaluation of a random (spot) stool sample. The spot stool sample can be assessed for blood by means of a stool guaiac test (e.g., Hemoccult slide). The presence of blood suggests an inflammatory or neoplastic cause for the diarrhea, but occult blood also can be seen in celiac disease and other sprue like syndromes. The presence of pus in the stool indicates an inflammatory cause of diarrhea. This can be assessed by staining a stool smear with Wright's stain and looking for white blood cells. A latex agglutination test for the neutrophil enzyme, lactoferrin, is of proven value for detecting neutrophils in acute infectious diarrheas and in pseudomembranous colitis. Its value in chronic diarrhea has not yet been assessed.

Diarrhea that contains neither blood, pus or fat is categorized as being watery diarrhea. This usually indicates a problem with the intestinal absorption of salt and water, and can be due to secretory states or to osmotic diarrheas.

Ultrasound examination and abdominal CT scan have a limited role in the evaluation of chronic diarrhea. Endoscopy usually is more specific than Xray studies because it allows direct inspection of the mucosa, detection of superficial lesions, and the ability to biopsy the mucosa. Upper endoscopy facilitates small bowel mucosal biopsy, which is essential in establishing the diagnosis of proximal small bowel diseases, most commonly celiac sprue, but also Whipple's disease and Crohn's disease. In immune suppressed patients, the diagnosis of parasitic infestation, e.g. microsporidia, cryptosporidia, Isospora belli, as well as cytomegalovirus infection can be made by small bowel biopsy.

Giardia lamblia can cause chronic diarrhea and usually is detected in stool specimens. Occasionally, however, the organism is identified in a small bowel biopsy or by a string test. The latter examination utilizes a swallowed string to obtain a specimen of mucus from the duodenal lumen, and the mucus is subsequently examined for the presence of the organism. This test is particularly helpful in evaluation of children in whom the risks and discomforts of endoscopy may not be well tolerated.

Other blood tests that can be of use include thyroid stimulating hormone, anti-nuclear antibody, anti-gliadin and anti-endomysial antibodies for celiac disease, perinuclear antineutrophil cytoplasmic antibodies (pANCA) for IBD, HLA typing, quantization of serum immunoglobulin levels, and serum antibodies against human immunodeficiency virus and Entamoeba histolytica.

A stool pH of less than 5.3 suggests carbohydrate malabsorption, because colonic bacteria produce short chain fatty acids from malabsorbed carbohydrate. If stool pH is greater than 5.6, it is unlikely that carbohydrate malabsorption by itself explains the diarrhea. Generalized malabsorption can produce stool pH greater than 5.3, however, because of buffering by other substances. Surreptitious laxative abuse continues to be an important and underappreciated cause of chronic diarrhea. Laxative screening includes tests for magnesium, phosphate and sulfate in stool water or urine.

When a specific diagnosis is made, specific treatment often can afford a cure of chronic diarrhea. Some experts recommend that patients should receive antibiotic therapy with metronidazole or antibiotics directed against enteric pathogens before any evaluation of chronic diarrhea is started. For most patients who have been evaluated to some extent, several other options are recommended. These include use of opiate antidiarrheal drugs, the somatostatin analogue, octreotide, and intraluminal agents, such as clays, charcoal, bile acid binding resins, bismuth compounds, and fiber.

Antimotility agents and opiates are the most effective empiric therapy for diarrhea. They not only relieve symptoms of frequency and urgency, but also reduce stool weight. Many patients respond to diphenoxylate or loperamide, but patients who do not respond to these therapies should be not be denied more potent opiates, such as codeine, opium, or morphine, for fear of addiction.