Acute and Chronic Diarrhea Dr.Atakan Yeşil Yeditepe University Department of Gastroenterology

Definitions Acute diarrhea <14 days duration Persistent diarrhea >14 days Chronic diarrhea >30 days Inflammatory diarrhea fever, tenesmus, fecal leukocytes, colonic bleeding Non-inflammatory diarrhea

Principles of Evaluation Majority of cases resolve in 1-2 days without any sequelae Stool culture has a low yield Specific diagnosis is useful for antimicrobial treatment decisions but not supportive treatment

Acute Diarrhea Subtypes Organik (Nonfunctional) Noninflammatory: Norwalk, Rota, Giardia, Staf. Aureus, B. Cereus, C. Perfringens, ETEC, Vibrio cholerae İnflammatory: CMV, EHEC, C. Difficile, Shigella, Salmonella, EIEC, Yersinia, E. Hystolytica İnorganik (Fonctunial)

The Big 4 found on 233,000 stool cultures Camphylobacter % Salmonella % Shigella % E coli O157:H7 (STEC) % Total yield from stool cultures is 5.8%

Other agents Norwalk virus Norovirus CMV (HIV, elderly) Various E coli strains (traveller’s diarrhea) Vibrio (shellfish, water) Giardia (persistent diarrhea) Cryptosporidium (farms) Isosporia Entamoeba histolytica Cyclospora Yersinia (lymphadenitis) Aeromonas

Clostridium difficile causes antibiotic-associated colitis; it colonizes the human intestinal tract after the normal gut flora have been altered by antibiotic therapy. It is one of the most common healthcare-associated infections and a significant cause of morbidity and mortality among elderly hospitalized patients.

Clinical Presentation Asymptomatic (carrier state) Antibiotic-associated diarrhea Antibiotic-associated colitis +/-Pseudomembranes profuse, watery-semi-formed stools mucoid - heme + systemic symptoms common marked abdominal tenderness hypoalbuminemia elevated WBC Ileus - toxic megacolon no diarrhea acute abdomen shock

Carrier state About 20 percent of hospitalized adults are C. difficile carriers who shed C. difficile in their stools but do not have diarrhea; in long-term care facilities, carriage rate may approach 50 percent. Although asymptomatic, these individuals serve as a reservoir for environmental contamination. The host immune response to C. difficile may play a role in determining an individual's carrier status. Data on treatment of asymptomatic carriers are limited and routine treatment is not recommended

C. difficile–associated diarrhea Manifestations of C. difficile–associated diarrhea with colitis include watery diarrhea up to 10 or 15 times daily with lower abdominal pain and cramping, low grade fever, and leukocytosis . Fever (T>38.5) is a sign of severe C. difficile–associated diarrhea (CDAD); fever is associated with CDAD in about 15 percent of cases. Leukocytosis in the setting of CDAD is common; Infrequently, symptoms present as late as 10 weeks after cessation of therapy

The antibiotics most frequently implicated in predisposition to C The antibiotics most frequently implicated in predisposition to C. difficile infection are fluoroquinolones, clindamycin, cephalosporins, and penicillins, but virtually all antibiotics, including metronidazole and vancomycin, can predispose to C. difficile

Physical examination generally demonstrates lower abdominal tenderness Physical examination generally demonstrates lower abdominal tenderness. Sigmoidoscopic or colonoscopic examination may demonstrate a spectrum of findings, from patchy mild erythema and friability to severe pseudomembranous colitis Unexplained leukocytosis in hospitalized patients (even in the absence of diarrhea) may reflect underlying C. difficile infection.

The diagnosis of C. difficile infection requires the presence of moderate to severe diarrhea or ileus, and either ●A stool test positive for C. difficile toxins or toxigenic C. difficile ●Endoscopic or histologic findings of pseudomembranous colitis

Diagnostic Tests for C. difficile Culture -Sensitivity nearly 100% -Specificity good if confirm toxin Manual Cytotoxin -Sensitivity and specificity nearly 100% EIA toxin test - sensitivity 90%

Treatment

What to do? Individual patient: In general Treat with Flagyl for 10 days Reserve Vancomycin for critically ill or allergic In general Try to use Flagyl instead of Clindamycin for anaerobic coverage Limit broad spectrum antibiotics C. difficile patients gloves private rooms, if possible

Recommended by AGA; obtaining stool cultures on initial presentation in immunocompromised patients (HIV-infected, elderly, patients with comorbidities or with underlying inflammatory bowel disease), those with severe or bloody diarrhea.

The management of patients with acute diarrhea begins with general measures such as hydration and alteration of diet. AGA recommends no antibiotic therapy in most cases

If empiric therapy is warranted, we recommend treatment with a fluoroquinolone for three to five days in the absence of suspected EHEC infection. If campylobacter is suspected we recommend azithromycin or erythromycin as alternative agents, given high rates of fluoroquinolone resistance. Directed antibiotic therapy should be administered when an intestinal pathogen is identified.

AGA suggests the antimotility agent loperamide be used for the symptomatic treatment of patients with acute diarrhea in whom fever is absent or low grade and the stools are not blood

Chronic Diarrhea Its definition has traditionally been based upon the frequency, volume, and consistency of stools. American Gastroenterological Association suggests that chronic diarrhea should be defined as a decrease in fecal consistency lasting for four or more weeks.

Irritable bowel syndrome Patients with IBS can present with a wide array of symptoms, which include both gastrointestinal and extraintestinal complaints. 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.

Functional diarrhea Functional diarrhea has been classified separately from IBS in a consensus statement (Rome III), which defines it as continuous or recurrent passage of loose (mushy) or watery stools without abdominal pain or discomfort

Inflammatory bowel disease Inflammatory bowel disease primarily refers to ulcerative colitis and Crohn disease.

Microscopic colitis Microscopic colitis is characterized by chronic watery (secretory) diarrhea without bleeding. It usually occurs in middle-aged patients but can affect childrenTwo 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 Lactose intolerance Chronic pancreatitis Celiac disease Bacterial overgrowth of the small intestine

Post-Cholecystectomy Diarrhea following cholecystectomy has been reported in 5 to 12 percent of patients

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

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 usually unnecessary, 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 .

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 ("Zollinger-Ellison syndrome (gastrinoma): 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.

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). 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) Breath testing can also identify specific forms of carbohydrate malabsorption (such as fructose or sucrose) but is rarely required. 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.

Inflammatory or infectious diarrhea Inflammatory diarrhea should be suspected in patients with clinical features suggesting inflammatory bowel disease 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. 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 noninflammatory 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.

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 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 . 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 . Fecal calprotectin levels are increased in intestinal inflammation and may be useful for distinguishing inflammatory from noninflammatory causes of chronic diarrhea . 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 and monitoring of activity in inflammatory bowel disease . However, its test characteristics are not yet sufficiently defined for routine clinical application for of these indications