Brief Answer: It is a diagnosis of exclusion - no specific test Detailed Answer: Hello and welcome, Habba Syndrome is a relatively new concept and I cannot find much about it in the research literature. The first paper on it was in 2000. There does not appear to be much about diagnostic standards for evaluating Habba Syndrome in the literature. From what I can find, other pathologies are ruled out in making this diagnosis, so it is a diagnosis of exclusion. Irritable bowel syndrome is also a diagnosis of exclusion (i.e. other things have been ruled out and so it is labeled as IBS, possibly because we don't have enough information in medicine yet to understand what various causes there may be for IBS). So there really isn't any specific definitive test that diagnosis Habba Syndrome that I can find. Diseases which should be ruled out include gluten intolerance/Celiac disease and other diseases of malabsorption, ulcerative colitis, Crohn's disease, gastrointestinal infections. So there should be stool studies, blood work, and colonoscopy. I am sharing an article from "Up To Date" which provides a summary of current standards on specific medical topics. It is lengthy, but may provide information that may help in your search for information on this. You will find a brief mention of Habba Syndrome and the reference article on it under the section on "Secretory Diarrhea". I would be happy to help interpret any questions you might have about the article. ----------------------------------- ----------------------------------- From Up To Date: Approach to the adult with chronic diarrhea in resource-rich settings Authors:Peter A L Bonis, MDJ XXXXXXX XXXXXXX MDSection Editor:Paul Rutgeerts, MD, PhD, FRCPDeputy Editor:Shilpa XXXXXXX MD, MPH, AGAF Contributor Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Oct 2017. | This topic last updated: Jun 05, 2017. INTRODUCTION — Diarrhea, derived from the Greek "to flow through," is a common manifestation of gastrointestinal disease. Its definition has traditionally been based upon the frequency, volume, and consistency of stools. However, the relationship between these features and patients' perception of diarrhea is variable. As a result, a consensus statement issued by the XXXXXXX Gastroenterological Association suggests that chronic diarrhea should be defined as three or more loose or watery stools daily lasting for four or more weeks. This topic review will provide an overview of the evaluation and treatment of chronic diarrhea. Individual disorders associated with chronic diarrhea, a discussion regarding diarrhea in HIV-infected patients, and an approach to patients with acute diarrhea are presented separately. (See "Evaluation of the HIV-infected patient with diarrhea" and "Approach to the adult with acute diarrhea in resource-rich settings".) EPIDEMIOLOGY — The prevalence of chronic diarrhea in the general population in developed nations has not been well established. The variable rates observed in several studies reflect differences in study design, definitions, and characteristics of populations that have been sampled [1-4]. Based upon a commonly used definition (ie, the presence of excessive stool frequency) a reasonable approximation is that chronic diarrhea affects approximately 5 percent of the population. Economic impact — The economic impact of chronic diarrhea has not been well quantified, particularly when considering societal costs. One estimate based upon limited data is that chronic diarrhea costs more than $350,000,000 annually from work loss alone [5,6]. Effect on quality of life — Chronic diarrhea can decrease quality of life. However, accurate assessment of the degree to which this occurs has not been established. One explanation is that a well-validated, disease-specific quality-of-life instrument has not yet been developed. Furthermore, no studies have attempted to measure quality of life in large groups of patients. Chronic diarrhea was an independent predictor of decreased quality of life in HIV-infected patients [7,8]. ETIOLOGY As a general rule, the principal causes of diarrhea depend upon the socioeconomic status of the population. In developing countries, chronic diarrhea is frequently caused by chronic bacterial, mycobacterial, and parasitic infections, although functional disorders, malabsorption, and inflammatory bowel disease are also common. In developed countries, common causes are irritable bowel syndrome (IBS), inflammatory bowel disease, malabsorption syndromes (such as lactose intolerance and celiac disease), and chronic infections (particularly in patients who are immunocompromised). The following sections will highlight the clinical features that should raise suspicion for some of the common disorders. Discussions on other disorders associated with chronic diarrhea are presented separately in the corresponding topic reviews. Irritable bowel syndrome and other functional bowel disorders — Patients with IBS can present with a wide array of symptoms, which include both gastrointestinal and extraintestinal complaints. However, the symptom complex of chronic lower abdominal pain and altered bowel habits remains the nonspecific yet primary characteristic of IBS. Patients usually experience the onset of symptoms as young adults, but the prevalence is similar in older adults. Females are diagnosed more than twice as often as males. Symptoms of IBS often correlate with episodes of psychologic stress. Thus, patients often seek medical help for their chronic symptoms during such periods. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".) Patients with IBS complain of crampy lower quadrant pain with diarrhea, constipation, alternating diarrhea and constipation, or normal bowel habits alternating with either diarrhea and/or constipation. Pain may be relieved with defecation. Diarrhea is usually characterized as frequent loose stools of small to moderate volume. Stools generally occur during waking hours, most often in the morning or after meals. Most bowel movements are preceded by extreme urgency and may be followed by a feeling of incomplete evacuation. Incontinence of liquid stool may occur during periods of disease activity. Post-infectious IBS can occur following recovery from Clostridium difficile and other bacterial infections. This condition may mimic the symptoms of the original infection with diarrhea and crampy pain. Patients who develop this condition are more likely to have had mild symptoms of IBS prior to the inciting infection.(See "Pathophysiology of irritable bowel syndrome".) Approximately one-half of all patients with IBS complain of mucus discharge with stools. Large volume diarrhea, bloody stools, nocturnal diarrhea, and greasy stools are not associated with IBS and suggest an organic disease. A diagnosis of IBS can be made if typical clinical findings are present, and does not necessarily require an exhaustive diagnostic evaluation. A number of related functional bowel disorders have also been described including functional diarrhea, IBS with predominant diarrhea, and IBS with mixed bowel habits. These disorders are considered to represent a continuum rather than being independent entities according to a consensus of experts [9]. Medications — Many drugs can cause diarrhea through a variety of mechanisms [10-12]. It can be challenging to identify the agent causing drug-induced diarrhea, particularly in patients taking multiple medications. The clinical setting and timing of the onset of symptoms relative to when the medications were started can be helpful. Inflammatory bowel disease — Inflammatory bowel disease primarily refers to ulcerative colitis and Crohn disease, although other intestinal disorders are also associated with intestinal inflammation. Most cases of ulcerative colitis and Crohn disease have their onset between ages 15 and 40. Many studies suggest a bimodal age distribution for both disorders with a second peak between age 50 and 80. IBD tends to run in families and is more common in Jews. (See "Definition, epidemiology, and risk factors in inflammatory bowel disease".) Crohn disease — Crohn disease may involve the entire gastrointestinal tract from mouth to perianal area. Diarrhea, abdominal pain, weight loss, and fever are the typical clinical manifestations for most patients with ileitis, ileocolitis, or Crohn colitis. Patients can have symptoms for many years prior to diagnosis. Although Hemoccult-positive stools are common in Crohn disease, gross bleeding is much less frequent than in ulcerative colitis (except for some patients with Crohn colitis). Ulcerative colitis — Patients with ulcerative colitis may present in a variable manner. For therapeutic and prognostic purposes, it has been useful to classify these presentations as mild, moderate, or severe. The severity of the symptomatology often correlates with the anatomic extent of disease, another parameter that will guide therapy. (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults".) ●Mild disease – Patients whose disease is confined to the rectum (proctitis) or rectosigmoid (proctosigmoiditis or distal colitis) often present insidiously with intermittent rectal bleeding associated with the passage of mucus, and the development of mild diarrhea with fewer than four small loose stools per day. Mild crampy pain, tenesmus, and periods of constipation are also common, but severe abdominal pain, profuse bleeding, fever, and weight loss are not part of the spectrum of mild disease. ●Moderate disease – Moderate disease is usually characterized anatomically by involvement of more than the distal colon, with the inflammatory process extending to at least the splenic flexure (left-sided colitis). The clinical picture is characterized by frequent loose, bloody stools (up to 10 per day), mild anemia not requiring blood transfusions, abdominal pain that is not severe, and low grade fever. Adequate nutrition is usually maintained. ●Severe disease – Patients with a severe or fulminant presentation usually have extensive colonic involvement, often but not always extending to the cecum (pancolitis). These patients typically have frequent loose stools (greater than 10 per day) with severe cramps, fever up to 39.5°C, and bleeding often necessitating blood transfusion. They may suffer rapid weight loss, leading to a poor nutritional state. The history is typically one of the gradual onset of symptoms, sometimes preceded by a self-limited episode of rectal bleeding that occurred weeks or months earlier. The initial episode is limited to the rectum or distal colon in one-third of patients, to the left colon up to the splenic flexure in one-third, and most of the remaining patients have pancolitis. Less than 10 percent present with fulminant disease. Physical examination is often normal at presentation. Among the findings that may be seen are pallor, evidence of weight loss, abdominal tenderness, and red blood on the examining finger on rectal examination. (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults".) Microscopic colitis — Microscopic colitis is characterized by chronic watery (secretory) diarrhea without bleeding. It usually occurs in middle-aged patients but can affect children. (See "Lymphocytic and collagenous colitis (microscopic colitis): Clinical manifestations, diagnosis, and management".) Two different types of microscopic colitis have been generally recognized: ●Lymphocytic colitis ●Collagenous colitis without lymphocytic infiltration of the surface epithelium Collagenous and lymphocytic colitis produce a similar clinical picture characterized by nonbloody chronic watery (secretory) diarrhea of up to two liters daily. The clinical course is mainly intermittent. The term microscopic colitis implies that the diagnosis is made by histology. Thus, colonoscopy usually reveals macroscopically normal colonic mucosa although slight edema, erythema, and friability may be seen. Although specimens obtained by flexible sigmoidoscopy are frequently sufficient to establish the diagnosis, the severity of histologic changes declines from the proximal to the distal colon; thus, biopsies obtained from the right colon (ie, by colonoscopy) are optimal. Malabsorption syndromes — Malabsorption refers to impaired absorption of nutrients. It can result from congenital defects in the membrane transport systems of the small intestinal epithelium (primary malabsorption) or from acquired defects (such as Crohn disease, celiac disease, or after extensive surgical resection or intestinal bypass operations) in the epithelial absorptive surface (secondary malabsorption). Another factor that can interfere with nutrient absorption is maldigestion due to impaired digestion of nutrients within the intestinal lumen (eg, exocrine pancreatic insufficiency) or at the terminal digestive site of the brush border membrane of mucosal epithelial cells (eg, lactose maldigestion). (See "Clinical features and diagnosis of malabsorption".) The clinical and laboratory features of malabsorption depend upon the cause and severity of the disease (table 1). As an example, isolated forms of malabsorption may present solely with symptoms that are attributable to the particular nutrient in question (table 2). The classic manifestations of malabsorption are pale, greasy, voluminous, foul-smelling stools, and weight loss despite adequate food intake. However, this spectrum of findings is relatively uncommon, even in generalized mucosal disease. The majority of patients with malabsorption have relatively mild gastrointestinal symptoms, which often mimic more common disorders such as irritable bowel syndrome. In some cases, anorexia, flatulence, abdominal distension, and borborygmi may be the only complaints suggesting malabsorption; other patients may be asymptomatic. Iron deficiency anemia may be the only clue to the presence of celiac disease (table 3). (See "Pathogenesis, epidemiology, and clinical manifestations of celiac disease in adults".) Relatively common disorders associated with malabsorption include: ●Lactose intolerance (see "Lactose intolerance: Clinical manifestations, diagnosis, and management") ●Chronic pancreatitis (see "Clinical manifestations and diagnosis of chronic pancreatitis in adults") ●Celiac disease (see "Pathogenesis, epidemiology, and clinical manifestations of celiac disease in adults") ●Bacterial overgrowth of the small intestine (see "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis") Post-cholecystectomy diarrhea — Diarrhea following cholecystectomy has been reported in 5 to 12 percent of patients [13-16]. In many cases the diarrhea will resolve or significantly improve over the course of weeks to months [13]. The diarrhea is related to excessive bile acids entering the colon [17,18]. In the absence of a gallbladder, bile drains directly and more continuously into the small bowel, which may overcome the terminal ileum's reabsorptive capacity. The increased bile acids in the colon lead to diarrhea (cholerheic diarrhea). Patients often respond to treatment with bile-acid binding resins such as cholestyramine or colestipol. Cholestyramine doses of up to 4 g daily have been suggested for the treatment of chronic diarrhea [19], though it is reasonable to start patients on a lower dose (eg, 2 g once or twice daily) and titrate to a higher dose as needed. We have found that patients often prefer pill formulations (eg, colestipol) over the powder (eg, cholestyramine). Chronic infections — Some persisting infections (eg, C. difficile, Aeromonas, Plesiomonas, Campylobacter, Giardia, Amebae, Cryptosporidium, Whipple's disease, and Cyclospora) can be associated with chronic diarrhea. (See appropriate topic reviews). These diagnoses should be considered in patients with specific risk factors such as travel, HIV infection, use of antibiotics, and consumption of potentially contaminated drinking water. All patients should be asked about use of antibiotics within the last three months. Several other causes of chronic diarrhea caused by, or resulting from a presumed infection have been described: ●An epidemic form of secretory diarrhea (Brainerd diarrhea) associated with patchy lymphocytic colonic inflammation can cause symptoms that persist for up to three years [20-25]. Risk factors include consumption of contaminated water and unpasteurized milk. An infectious agent is suspected but has not been identified. ●The development of post-infectious irritable bowel syndrome has also been described in up to 30 percent of patients following documented acute bacterial enteric infections. (See "Pathophysiology of irritable bowel syndrome".) ●It is possible that some patients with chronic diarrhea may have an infectious cause that may not be easily demonstrable. A case report described a woman with severe, debilitating diarrhea that was ultimately found to be due to Stenotrophomonas maltophilia, a Gram-negative rod that was only identifiable using molecular genetic techniques [26]. Further studies using such techniques will help determine whether other infectious agents can be implicated in chronic diarrhea. ●Chronic diarrhea due to Candida albicans infection has been described in case reports [27]. Most patients had received immunosuppression (in some cases with antibiotics), were malnourished, or had an immune disorder [27]. Diagnosis was established by detection of large numbers of Candida in small bowel aspirates and stool specimens and response to antifungal therapy. The presence of Candida in stool specimens has also been described in asymptomatic individuals and thus the clinical context is important in considering the diagnosis. ●Chronic infection with Blastocystis hominis, an anaerobic protozoan parasite, has been implicated as a cause of chronic diarrhea in some reports. (See "Blastocystis species".) EVALUATION — Optimal strategies for the evaluation of patients with chronic diarrhea have not been established. Recommendations have been derived mostly from expert opinion and from experience in individual clinical centers, both of which are vulnerable to bias. However, a specific diagnosis can be achieved in more than 90 percent of patients. The selection of specific tests, timing of referral, and the extent to which testing should be performed depend upon an appraisal of the likelihood of a specific diagnosis, the availability of treatment, the severity of symptoms, patient preference, and comorbidities. Timing of referral — The timing of referral to a subspecialist depends upon the severity of symptoms, the diagnoses being considered, and the need for and availability of endoscopic procedures. As an example, referral may be unnecessary in a young patient with typical symptoms of irritable bowel syndrome (IBS) while it should be considered sooner in a patient in whom inflammatory bowel disease (IBD) is suspected. Referral should also be considered in patients in whom a diagnosis that requires long-term management (eg, IBD, chronic pancreatitis) has been established. History — A thorough medical history can guide appropriate evaluation. Important components of the history include (table 4): ●A clear understanding of what led the patient to complain of diarrhea (eg, consistency or frequency of stools, the presence of urgency or fecal soiling). ●Stool characteristics (eg, greasy stools that float and are malodorous may suggest fat malabsorption, while the presence of visible blood may suggest IBD). ●Duration of symptoms, nature of onset (sudden or gradual). ●Travel history. ●Risk factors for HIV infection. ●Weight loss. ●Whether there is fecal incontinence (which may be confused with diarrhea). ●Occurrence of diarrhea during fasting or at night (suggesting a secretory diarrhea). ●Family history of IBD. ●The volume of the diarrhea (eg, voluminous watery diarrhea is more likely to be due to a disorder in the small bowel while small-volume frequent diarrhea is more likely to be due to disorders of the colon). ●The presence of bloody diarrhea favors a colonic versus small bowel disorder. ●The presence of systemic symptoms, which may indicate IBD (such as fevers, joint pains, mouth ulcers, eye redness). ●All medications (including over-the-counter drugs and supplements) (table 5). ●A relevant dietary (including possible use of sorbitol-containing products and use of alcohol). ●Association of stress and depression with onset and severity of the diarrhea. ●Association of symptoms with specific food ingestion (such as dairy products or potential food allergens). ●A sexual history (anal intercourse is a risk factor for infectious proctitis and promiscuous sexual activity is a risk factor associated with HIV infection). ●A history of recurrent bacterial infections (eg, sinusitis, pneumonia), which may indicate a primary immunoglobulin deficiency (see "Clinical manifestations, epidemiology, and diagnosis of common variable immunodeficiency in adults"). Physical examination — The physical examination rarely provides a specific diagnosis. However, a number of findings can provide clues. These include findings suggestive of IBD (eg, mouth ulcers, a skin rash, episcleritis, an anal fissure or fistula, the presence of visible or occult blood on digital examination, abdominal masses or abdominal pain), evidence of malabsorption (such as wasting, physical signs of anemia, scars indicating prior abdominal surgery), lymphadenopathy (possibly suggesting HIV infection), and abnormal anal sphincter pressure or reflexes (possibly suggesting fecal incontinence). The presence of tympany on abdominal percussion with or without distention can be a clue to IBS or malabsorption. Palpation of the thyroid and examination for exophthalmos and lid retraction may provide support for a diagnosis of hyperthyroidism. Specific testing — A large number of tests are available for diagnosing specific causes of diarrhea. Characteristics and performance of the tests are discussed in the individual topic reviews dealing with the various disorders (see appropriate topic reviews). There is no firm rule as to what testing should be done. The history and physical examination may point toward a specific diagnosis for which testing may be indicated. As an example, serologic testing for celiac disease would be appropriate in patients with risk factors (such as type 1 diabetes mellitus or a family history of celiac disease) or those with unexplained iron deficiency anemia or weight loss from fat malabsorption (see "Diagnosis of celiac disease in adults"). Diarrhea in patients with diabetes may also be due to visceral autonomic neuropathy, pancreatic exocrine insufficiency, bacterial overgrowth, or fecal incontinence (which may be confused with diarrhea). (See appropriate topic reviews). The minimum laboratory evaluation in most patients should include a complete blood count and differential, erythrocyte sedimentation rate, C-reactive protein, thyroid function tests, serum electrolytes, total protein and albumin, and stool occult blood. In addition, most patients require some form of endoscopic evaluation and mucosal biopsy (either colonoscopy or sometimes upper endoscopy), depending upon the clinical setting. (See 'Colonoscopy versus sigmoidoscopy' below.) Because irritable bowel syndrome is one of the most common causes of chronic diarrhea, it is frequently useful to begin evaluation by attempting to categorize the symptoms and signs of the diarrhea as more likely to be either functional (related to IBS) or organic (related to an identifiable bowel pathology). As discussed above, the diagnosis of IBS should be sought actively by inquiring about characteristic features. The presence of significant weight loss, anemia, occult or overt gastrointestinal bleeding, or nocturnal awakening with pain or diarrhea are inconsistent with IBS and should alert to other diagnoses. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".) Another useful way to guide specific testing is to attempt to categorize diarrhea as watery, inflammatory, or fatty (algorithm 1). Those with watery diarrhea can be subcategorized further as having secretory or osmotic diarrhea (calculator 1). These distinctions can sometimes be suggested based upon the medical history. The diagnosis can then be confirmed by focused testing. Secretory diarrhea — Secretory diarrhea characteristically continues despite fasting, is associated with stool volumes >1 liter/day, and occurs day and night in contrast to osmotic diarrhea in which these characteristics are uncommon. Although seldom required, the distinction between an osmotic and a secretory diarrhea can also be established by measuring stool electrolytes and calculating an osmotic gap. The osmotic gap is determined by subtracting the sum of the sodium and potassium concentration in stool multiplied by a factor of 2 from 290 mOsm/kg to account for unmeasured anions (ie, 290 - 2 ({Na+} + {K+})) (calculator 1). An osmotic gap of >125 mOsm/kg suggests an osmotic diarrhea while a gap of <50 mOsm/kg suggests a secretory diarrhea [28]. Further testing in patients with secretory diarrhea may include stool cultures to exclude chronic infection, imaging of the small and large bowel, and selective testing for secretagogues, such as gastrin or vasoactive intestinal polypeptide (algorithm 2) (see "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis" and "VIPoma: Clinical manifestations, diagnosis, and management"). Secretory diarrhea occurs in 80 percent of patients with carcinoid syndrome and is often the most debilitating component of the syndrome. Stools may vary from few to more than 30 per day, are typically watery and nonbloody, and can be explosive and accompanied by abdominal cramping. The abdominal cramps may be a consequence of mesenteric fibrosis or intestinal blockage by the primary tumor. The diarrhea is usually unrelated to flushing episodes. (See "Clinical features of the carcinoid syndrome".) Testing for bile-acid malabsorption or empiric treatment with a bile-acid binding resin may also be helpful. An association between bile acid malabsorption and gallbladder dysmotility has been described (Habba syndrome) [29]. The diarrhea responds to cholestyramine. Further testing in patients with osmotic diarrhea may be unnecessary if the osmotic agent can be identified based upon the history. An example is inadvertent ingestion of sorbitol (such as in sugar substitutes) or lactose in patients who have lactose intolerance. Temporary avoidance of lactose-containing foods can help establish the diagnosis of lactose intolerance in patients who were unaware of the diagnosis. As an alternative, the diagnosis can be made by specific testing for lactose intolerance (such as hydrogen breath testing) (see "Lactose intolerance: Clinical manifestations, diagnosis, and management"). Breath testing can also identify specific forms of carbohydrate malabsorption (such as fructose or sucrose) but is rarely required (table 6). Testing the stool for laxatives may occasionally be required if laxative abuse is suspected. Laxative abuse can be suggested by the presence of melanosis coli on sigmoidoscopy or colonoscopy. Tests for bacterial overgrowth should be performed in patients with risk factors (table 7) (see "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis"). Clinical or laboratory features suggesting malabsorption should prompt a specific evaluation (table 1 and table 2 and table 3). (See "Clinical features and diagnosis of malabsorption".) Inflammatory or infectious diarrhea — Inflammatory diarrhea should be suspected in patients with clinical features suggesting inflammatory bowel disease (see 'Inflammatory bowel disease' above), C. difficile infection, those at risk for opportunistic infections such as tuberculosis, or those with a pertinent travel history. Diagnosis can usually be established by sigmoidoscopy or colonoscopy or by analysis of stool specimens (ie, stool testing for C. difficile toxins or their genes). Barium enema is seldom used in the evaluation of diarrhea, and has been largely replaced by endoscopy and biopsy. Serum markers of acute inflammation (such as the sedimentation rate and C-reactive protein levels) are useful in identifying patients with suspected inflammatory diarrhea. These markers are typically normal in patients with non-inflammatory chronic diarrhea such as IBS or food intolerance. However, their test characteristics have not been well validated for this purpose; thus, their role in patients presenting with chronic diarrhea is unclear. (See "Acute phase reactants" and "Clinical manifestations, diagnosis and prognosis of Crohn disease in adults".) Several stool studies have also been evaluated for identifying patients with inflammatory diarrhea [30]. Fecal leukocytes — A number of studies have evaluated the accuracy of fecal leukocytes alone or in combination with occult blood testing. The ability of these tests to predict the presence of an inflammatory diarrhea has varied greatly, with reports of sensitivity and specificity ranging from 20 to 90 percent [31-34]. A meta-analysis of diagnostic test accuracy estimated that at a peak sensitivity of 70 percent, the specificity of fecal leukocytes was only 50 percent [34]. Thus, fecal leukocytes are not a good test for inflammatory diarrhea. Fecal calprotectin — Calprotectin is a zinc and calcium binding protein that is derived mostly from neutrophils and monocytes. It can be detected in tissue samples, body fluids, and stools, making it a potentially valuable marker of neutrophil activity [35]. Fecal calprotectin levels are increased in intestinal inflammation and may be useful for distinguishing inflammatory from noninflammatory causes of chronic diarrhea [36,37]. A meta-analysis of 13 studies of both adults and children with chronic diarrhea and/or suspected inflammatory bowel disease (IBD) who underwent endoscopy estimated sensitivity and specificity to discriminate IBD from other causes of symptoms [38]. In adults, pooled sensitivity was 93 percent (95% CI 0.85 to 0.97) and pooled specificity was 96 percent (95% CI 0.79 to 0.99). In children and teenagers, sensitivity was similar (92 percent, 95% CI 0.84 to 0.96) but specificity was significantly lower (76 percent, 95% CI 0.62 to 0.86). The authors note that in settings with a low prevalence of IBD (such as among patients seen for abdominal pain or diarrhea in a primary care setting) the test might be most useful to help rule out IBD while in high prevalence settings (such as a gastroenterology clinic) the test might be most useful for ruling in IBD. However, test characteristics varied considerably among the studies included in the meta-analysis. Furthermore, diagnostic evaluation (including endoscopy) is sometimes needed even if IBD is not strongly suspected. Thus, fecal calprotectin can be considered as an adjunctive test in diagnostic evaluation of patients with chronic diarrhea. Other potential roles have also been proposed including in colorectal cancer screening [39-41] and monitoring of activity in inflammatory bowel disease [42]. However, its test characteristics are not yet sufficiently defined for routine clinical application for of these indications. Fecal lactoferrin — Fecal lactoferrin (another marker of neutrophils) has also been proposed as an indicator of intestinal inflammation but its role in the evaluation of patients with chronic diarrhea remains uncertain [43]. Fatty diarrhea — Fatty diarrhea (steatorrhea) should be suspected in patients who report greasy, malodorous stools and those who are at risk for fat malabsorption, such as patients with chronic pancreatitis. A variety of tests can be used to confirm the diagnosis. Currently, the gold standard for diagnosis of steatorrhea is quantitative estimation of stool fat. (See "Clinical features and diagnosis of malabsorption" and "Exocrine pancreatic insufficiency".) Colonoscopy versus sigmoidoscopy — Many of the diagnoses discussed above require endoscopic imaging and biopsy of the colon. An endoscopic evaluation should be considered if there are persistent symptoms, inconclusive diagnosis, or failure to respond to therapy. Guidelines for the role of endoscopy in the management of patients with diarrhea have been published by the XXXXXXX Society of Gastrointestinal Endoscopy [44]. The recommendations here are consistent with these guidelines. An advantage of colonoscopy is that it permits examination and biopsy of the entire colon and the terminal ileum (in many patients). However, flexible sigmoidoscopy (to 60 cm) is often sufficient for establishing the diagnosis, is less expensive, and is associated with fewer risks. ●The major complication of sigmoidoscopy is perforation of the colon. The risk has been estimated to be 1 to 2 per 10,000 examinations in older series. Only two perforations in 109,534 examinations were reported among patients undergoing colorectal cancer screening at Kaiser Permanente Medical Center between 1994 and 1996 [45]. Overall, there were 24 complications, of which seven were considered to be serious. Mortality from flexible sigmoidoscopy is rare. ●Complications associated with colonoscopy include perforation, hemorrhage, respiratory depression due to sedation, arrhythmia, transient abdominal pain, ileus, and nosocomial infection. The most common serious complications are perforation (risk ranging from 0.01 to 0.3 percent in various reports) and bleeding (approximate risk 3 per 1000) [46]. The risk of death has been estimated to be 1 to 3 per 10,000. That sigmoidoscopy may be sufficient for diagnosis of chronic diarrhea has been illustrated in at least two studies. ●A study from XXXXXXX focused on 809 patients with chronic nonbloody diarrhea unassociated with HIV infection who underwent colonoscopy [47]. A suggestive finding or specific diagnosis was made in 15 percent, including (in descending order of frequency) microscopic colitis, Crohn disease, melanosis coli, ulcerative colitis, and other forms of colitis. The majority of findings (99.7 percent) were within reach of a flexible sigmoidoscope. ●A second study with 625 patients undergoing colonoscopy found abnormalities in 126 (20 percent) [48]. The most common abnormal finding was suspected mucosal inflammation (60 patients). Seventy-two percent of the abnormalities were within reach of a flexible sigmoidoscope and the overall sensitivity for flexible sigmoidoscopy and biopsy was estimated to be 85 percent. The sensitivity for detecting inflammatory bowel disease was 84 percent and the sensitivity for detecting microscopic colitis was 92 percent. Thus, a sigmoidoscopy may be a reasonable initial test for many patients. Exceptions are patients with iron deficiency anemia, those in whom inspection of the terminal ileum is desired (such as in the evaluation of Crohn disease), and older patients in whom a colonoscopy may have an added advantage of screening for polyps and colorectal cancer. In addition, approximately 10 percent of patients with collagenous colitis have findings only in the proximal colon [49,50]. Thus, a colonoscopy may be a better initial test if this diagnosis is being considered. (See "Lymphocytic and collagenous colitis (microscopic colitis): Clinical manifestations, diagnosis, and management".) Bowel imaging — Radiologic imaging of the GI tract in patients with chronic diarrhea provides important diagnostic information particularly those in whom small bowel and pancreatic disease are under consideration. Patients with abdominal pain as a major symptom in addition to chronic diarrhea often require imaging tests. Plain abdominal films in the supine and upright position can provide evidence of bowel distention or air-fluid levels suggesting a motility disease, megacolon due to infectious or inflammatory processes, or partial mechanical obstruction due to strictures in Crohn disease or tumors such as carcinoid. More detailed imaging of the small bowel and pancreas is provided by abdominal computed tomography or magnetic resonance imaging. (See "Clinical manifestations and diagnosis of chronic pancreatitis in adults", section on 'CT, MRI, and US' and "Clinical manifestations, diagnosis and prognosis of Crohn disease in adults", section on 'Imaging studies'.) Role of empiric therapy — As a general rule, some degree of diagnostic testing is indicated in patients with chronic diarrhea. However, empiric therapy may be warranted in certain situations, such as: ●When a diagnosis is strongly suspected. Examples include a daycare worker who develops diarrhea after a known outbreak of giardiasis within the daycare, a patient who develops diarrhea following limited (<100 cm) ileal resection in whom bile acid malabsorption is likely, a patient with known recurrent bacterial overgrowth, and an otherwise healthy patient with suspected lactose intolerance in whom relief of symptoms is observed following a temporary trial of a lactose-free diet. ●When comorbidities limit diagnostic evaluation. Symptomatic therapy — Symptomatic therapy is indicated when the diagnosis has been made but definitive treatment is unavailable, when diagnosis has eluded diagnostic evaluation, and as a temporizing measure during evaluation. A variety of medications can help relieve symptoms, including loperamide, anticholinergic agents, and intraluminal adsorbents (such as clays, activated charcoal, bismuth, fiber and bile acid binding resins). Their role in specific disorders is discussed in the corresponding topic reviews. INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) ●Beyond the Basics topics (see "Patient education: Chronic diarrhea in adults (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS — Chronic diarrhea should be defined as a decrease in fecal consistency lasting for four or more weeks. ●A myriad of disorders are associated with chronic diarrhea. The prevalence of specific disorders varies based upon the practice setting. In developed countries, common causes are irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), malabsorption syndromes (such as lactose intolerance and celiac disease), and chronic infections (particularly in patients who are immunocompromised). (See 'Etiology' above.) ●Optimal strategies for the evaluation of patients with chronic diarrhea have not been established. The selection of specific tests, timing of referral, and the extent to which testing should be performed depend upon an appraisal of the likelihood of a specific diagnosis, the availability of treatment, the severity of symptoms, patient preference, and comorbidities (algorithm 1). (See 'Evaluation' above.) ●A thorough medical history can guide appropriate evaluation (table 4). (See 'History' above.) ●The physical examination rarely provides a specific diagnosis. However, a number of findings can provide clues. These include findings suggestive of IBD (eg, mouth ulcers, a skin rash, episcleritis, an anal fissure or fistula, the presence of visible or occult blood on digital examination, abdominal masses or abdominal pain), evidence of malabsorption (such as wasting, physical signs of anemia, scars indicating prior abdominal surgery), lymphadenopathy (possibly suggesting HIV infection), and abnormal anal sphincter pressure or reflexes (possibly suggesting fecal incontinence). Palpation of the thyroid and examination for exophthalmos and lid retraction may provide support for a diagnosis of hyperthyroidism. (See 'Physical examination' above.) ●There is no firm rule as to what testing should be done. The history and physical examination may point toward a specific diagnosis for which testing may be indicated. As an example, serologic testing for celiac disease would be appropriate in patients with risk factors (such as type 1 diabetes mellitus or a family history of celiac disease) (see "Diagnosis of celiac disease in adults"). The minimum laboratory evaluation in most patients should include a complete blood count and differential, C-reactive protein and sedimentation rate, thyroid function tests, serum electrolytes, total protein and albumin, and stool occult blood. In addition, most patients require some form of endoscopic evaluation (either sigmoidoscopy, colonoscopy, or sometimes upper endoscopy) with biopsy and histopathologic evaluation depending upon the clinical setting. Radiologic imaging of the pancreas and small bowel is often required for small bowel inflammation, pancreatic tumors, and chronic pancreatic insufficiency. Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES Talley NJ, O'Keefe EA, Zinsmeister AR, Melton LJ 3rd. Prevalence of gastrointestinal symptoms in the elderly: a population-based study. Gastroenterology 1992; 102:895. Talley NJ, Zinsmeister AR, Van Dyke C, Melton LJ 3rd. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology 1991; 101:927. Talley NJ, Weaver AL, Zinsmeister AR, Melton LJ 3rd. Onset and disappearance of gastrointestinal symptoms and functional gastrointestinal disorders. Am J Epidemiol 1992; 136:165. Sandler RS, XXXXXXX WF, Liberman JN, et al. Abdominal pain, bloating, and diarrhea in the United States: prevalence and impact. Dig Dis Sci 2000; 45:1166. Fine KD, Schiller LR. AGA technical review on the evaluation and management of chronic diarrhea. Gastroenterology 1999; 116:1464. Everhart JE (Ed). Digestive Disease in the United States: Epidemiology and impact. NIH Publ 94-1447. Bethesda, MD: National Instiutues of Health, 1994. Lubeck DP, XXXXXXX CL, Mazonson PD, et al. Quality of life and health service use among HIV-infected patients with chronic diarrhea. J Acquir Immune Defic Syndr 1993; 6:478. Watson A, Samore MH, Wanke CA. Diarrhea and quality of life in ambulatory HIV-infected patients. Dig Dis Sci 1996; 41:1794. Schmulson MJ, Drossman DA. What Is New in Rome IV. J Neurogastroenterol Motil 2017; 23:151. XXXXXXX NA, XXXXXXX N, Pitchumoni CS. Spectrum of Drug-induced Chronic Diarrhea. J Clin Gastroenterol 2017; 51:111. Burbure N, Lebwohl B, Arguelles-Grande C, et al. Olmesartan-associated sprue-like enteropathy: a systematic review with emphasis on histopathology. Hum Pathol 2016; 50:127. Kroschinsky F, Stölzel F, von Bonin S, et al. New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management. Crit Care 2017; 21:89. Sauter GH, Moussavian AC, Meyer G, et al. Bowel habits and bile acid malabsorption in the months after cholecystectomy. Am J Gastroenterol 2002; 97:1732. Fort JM, Azpiroz F, Casellas F, et al. Bowel habit after cholecystectomy: physiological changes and clinical implications. Gastroenterology 1996; 111:617. Ros E, Zambon D. Postcholecystectomy symptoms. A prospective study of gall stone patients before and two years after surgery. Gut 1987; 28:1500. XXXXXXX RG, Macintyre IM. Symptomatic outcome after laparoscopic cholecystectomy. Br J Surg 1993; 80:439. Arlow FL, Dekovich AA, Priest RJ, Beher WT. Bile acid-mediated postcholecystectomy diarrhea. Arch Intern Med 1987; 147:1327. Breuer NF, Jaekel S, Dommes P, Goebell H. Fecal bile acid excretion pattern in cholecystectomized patients. Dig Dis Sci 1986; 31:953. Schiller LR. Chronic Diarrhea. Curr Treat Options Gastroenterol 2005; 8:259. XXXXXXX DA, Mintz ED, Puhr ND, et al. Colonic epithelial lymphocytosis associated with an epidemic of chronic diarrhea. Am J Surg Pathol 1996; 20:1102. Janda RC, Conklin JL, Mitros FA, Parsonnet J. Multifocal colitis associated with an epidemic of chronic diarrhea. Gastroenterology 1991; 100:458. Mintz ED, Weber JT, Guris D, et al. An outbreak of Brainerd diarrhea among travelers to the Galapagos Islands. J Infect Dis 1998; 177:1041. Osterholm MT, MacDonald KL, White KE, et al. An outbreak of a newly recognized chronic diarrhea syndrome associated with raw milk consumption. JAMA 1986; 256:484. Vugia DJ, Abbott S, Mintz ED, et al. A restaurant-associated outbreak of Brainerd diarrhea in California. Clin Infect Dis 2006; 43:62. Kimura AC, Mead P, Walsh B, et al. A large outbreak of Brainerd diarrhea associated with a restaurant in the Red River Valley, XXXXXXX Clin Infect Dis 2006; 43:55. Hellmig S, Ott S, Musfeldt M, et al. Life-threatening chronic enteritis due to colonization of the small bowel with Stenotrophomonas maltophilia. Gastroenterology 2005; 129:706. Friedman M, XXXXXXX DB, Borum ML. An unusual case report of small bowel Candida overgrowth as a cause of diarrhea and review of the literature. Dig Dis Sci 2007; 52:679. Eherer AJ, Fordtran JS. Fecal osmotic gap and pH in experimental diarrhea of various causes. Gastroenterology 1992; 103:545. Habba SF. Chronic diarrhea: identifying a new syndrome. Am J Gastroenterol 2000; 95:2140. Schoepfer AM, Trummler M, Seeholzer P, et al. Accuracy of four fecal assays in the diagnosis of colitis. Dis Colon Rectum 2007; 50:1697. Chitkara YK, McCasland KA, Kenefic L. Development and implementation of cost-effective guidelines in the laboratory investigation of diarrhea in a community hospital. Arch Intern Med 1996; 156:1445. Stoll BJ, Glass RI, Banu H, et al. Value of stool examination in patients with diarrhoea. Br Med J (Clin Res Ed) 1983; 286:2037. Siegel D, Cohen PT, Neighbor M, et al. Predictive value of stool examination in acute diarrhea. Arch Pathol Lab Med 1987; 111:715. Huicho L, Sanchez D, Contreras M, et al. Occult blood and fecal leukocytes as screening tests in childhood infectious diarrhea: an old problem revisited. Pediatr Infect Dis J 1993; 12:474. Poullis A, Foster R, Mendall MA, Fagerhol MK. Emerging role of calprotectin in gastroenterology. J Gastroenterol Hepatol 2003; 18:756. Holtman GA, Lisman-van Leeuwen Y, Reitsma JB, Berger MY. Noninvasive Tests for Inflammatory Bowel Disease: A Meta-analysis. Pediatrics 2016; 137. Mosli MH, Zou G, Garg SK, et al. C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2015; 110:802. van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ 2010; 341:c3369. Kristinsson J, Nygaard K, Aadland E, et al. Screening of first degree relatives of patients operated for colorectal cancer: evaluation of fecal calprotectin vs. hemoccult II. Digestion 2001; 64:104. Kristinsson J, Armbruster CH, Ugstad M, et al. Fecal excretion of calprotectin in colorectal cancer: relationship to tumor characteristics. Scand J Gastroenterol 2001; 36:202. Limburg PJ, Devens ME, Harrington JJ, et al. Prospective evaluation of fecal calprotectin as a screening biomarker for colorectal neoplasia. Am J Gastroenterol 2003; 98:2299. Bunn SK, Bisset WM, Main MJ, et al. Fecal calprotectin: validation as a noninvasive measure of bowel inflammation in childhood inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2001; 33:14. XXXXXXX SV, Sandborn WJ, Rufo PA, et al. Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. Am J Gastroenterol 2003; 98:1309. ASGE Standards of Practice Committee, Shen B, XXXXXXX K, et al. The role of endoscopy in the management of patients with diarrhea. Gastrointest Endosc 2010; 71:887. Levin TR, Conell C, Shapiro JA, et al. Complications of screening flexible sigmoidoscopy. Gastroenterology 2002; 123:1786. Korman LY, Overholt BF, Box T, Winker CK. Perforation during colonoscopy in endoscopic ambulatory surgical centers. Gastrointest Endosc 2003; 58:554. Fine KD, Seidel RH, Do K. The prevalence, anatomic distribution, and diagnosis of colonic causes of chronic diarrhea. Gastrointest Endosc 2000; 51:318. Shale MJ, Walters JR, Westaby D. Adequacy of flexible sigmoidoscopy with biopsy for diarrhea in patients under age 50 without features of proximal disease. Gastrointest Endosc 2011; 73:757. Tanaka M, Mazzoleni G, Riddell RH. Distribution of collagenous colitis: utility of flexible sigmoidoscopy. Gut 1992; 33:65. Zins BJ, XXXXXXX WJ, Carpenter HA. Collagenous colitis: mucosal biopsies and association with fecal leukocytes. Mayo Clin Proc 1995; 70:430.