Ahmad Hormati Assistant Professor of Gastroenterology Qom University

Ahmad Hormati Assistant Professor of Gastroenterology Qom University of Medical Sciences. Email: hormatia@yahoo. com http: //hormatigi. ir/

Approach to Diarrhea

Acute Diarrhea

Definitions � Diarrhea -working definition is: Ø three or more loose or watery stools per day or Ø definite decrease in consistency and increase in frequency based upon an individual baseline q. Acute — ≤ 14 days in duration q Persistent diarrhea — more than 14 days in duration q. Chronic — more than 30 days in duration

Introduction q One of the five leading causes of death worldwide q Most cases of acute diarrhea are due to infections with viruses and bacteria and are selflimited. � Noninfectious etiologies become more common as the course of the diarrhea persists and becomes chronic. Noninfectious causes of diarrhea include drugs, food allergies, primary gastrointestinal diseases such as inflammatory

q. Most cases of acute infectious gastroenteritis are probably viral, q. In contrast, bacterial causes are responsible for most cases of severe diarrhea

DIAGNOSTIC APPROACH qcareful history � Duration of symptoms � Frequency and characteristics of the stool. � Complete past medical history (identify immunocompromised host) � Important to ask about recent antibiotic use �A food history may also provide clues to a diagnosis: Ø Within 6 hr Staphylococcus aureus or Bacillus cereus Ø Within 8 to 16 hr Clostridium perfringens Ø More than 16 hr viral or bacterial infection ( enterotoxigenic or enterohemorrhagic E. coli).

q Physical examination: �fever, which suggests infection with : Ø invasive bacteria (Salmonella, Shigella, Campylobacter) Ø Enteric viruses, or Ø Cytotoxic organism such as Clostridium difficile or Entamoeba histolytica � Evidence of extracellular volume depletion (eg, decreased skin turgor, orthostatic hypotension

Bloody diarrhea �E. coli O 157: H 7 (Most common) �Less common bacterial causes : � Shigella, �Campylobacter, � Salmonella species

Fecal leukocytes and occult blood �Sensitivity and specificity ranging from 20 to 90 percent �Because of these concerns about test performance, the role of testing for fecal leukocytes has been questioned. � However, the presence of occult blood and fecal leukocytes supports the diagnosis of a bacterial cause of diarrhea Uptoate: we perform this examination in addition to obtaining a bacterial culture in high risk patients.

Lactoferrin �Lactoferrin is a marker for fecal leukocytes, but its measurement is more precise � sensitivity and specificity ranging from 90 to 100 percent in distinguishing inflammatory diarrhea (eg, bacterial colitis or inflammatory bowel disease) from noninflammatory causes (eg, viral colitis, irritable bowel syndrome)

When to obtain stool cultures low rate of positive stool cultures in most reports (1. 5 to 5. 6 percent) most infectious causes of acute diarrhea are self-limited it is reasonable to continue symptomatic therapy for several days before considering further evaluation

When to obtain stool cultures we recommend obtaining stool cultures on initial presentation in the following groups of patients: � Immunocompromised patients, including those infected with HIV � Patients with comorbidities that increase the risk for complications � Patients with more severe, inflammatory diarrhea (including bloody diarrhea) � Patients with underlying inflammatory bowel disease in whom the distinction between a flare and superimposed infection is critical � Some employees, such as food handlers

When to obtain stool for ova and parasites q Persistent diarrhea (associated with Giardia, Cryptosporidium, and Entamoeba histolytica) q Persistent diarrhea with exposure to infants in daycare centers(associated with Giardia and Cryptosporidium) q Diarrhea in a man who has sex with men (MSM) or a patient with AIDS (associated with Giardia and Entamoeba histolytica in the former, and a variety of parasites in the latter). q A community waterborne outbreak (associated with Giardia and Cryptosporidium) q Bloody diarrhea with few or no fecal leukocytes (associated with intestinal amebiasis) Three specimens should be sent on consecutive days (or each specimen separated by at least 24 hours)

TREATMENT �Begins with general measures such as hydration and alteration of diet. �Antibiotic therapy is not required in most cases since the illness is usually self-limited. �Oral rehydration solutions: �Oral rehydration solutions were developed following the realization that, in many small bowel diarrheal illnesses, intestinal glucose absorption via sodium-glucose cotransport remains intact.

�The composition of the oral rehydration solution (per liter of water) recommended by the World Health Organization consists of: � 3. 5 g sodium chloride � 2. 9 g trisodium citrate or 2. 5 g sodium bicarbonate � 1. 5 g potassium chloride � 20 g glucose or 40 g sucrose

Enterohemorrhagic E. coli q Antibiotics should be avoided in patients with suspected or proven infection with enterohemorrhagic E. coli (EHEC). why There is no evidence of benefit from antibiotic therapy for EHEC infection 2. there is concern about an increase in the risk of hemolytic-uremic syndrome that might be mediated by an increase in the production or release of Shiga toxin when antibiotics are administered q EHEC infection should be suspected in patients with bloody diarrhea, abdominal pain and tenderness, but little or no fever. 1.

Clostridium difficile q Patients with acute diarrhea should be questioned carefully about prior antibiotic therapy and other risk factors for C. difficile infection. q The appropriate therapy for this infection is: Discontinuation of antibiotics, if possible, 2. Consideration of metronidazole or vancomycin if the symptoms are more than mild or worsen or persist 1.

When to treat q Those with moderate to severe travelers' diarrhea as characterized by more than four unformed stools daily, fever, blood, pus, or mucus in the stool. q Those with more than eight stools per day q volume depletion q symptoms for more than one week q those in whom hospitalization is being considered q Immunocompromised hosts q Signs and symptoms of bacterial diarrhea such as fever, bloody diarrhea (except for suspected EHEC or C. difficile infection q Presence of occult blood or fecal leukocytes in the stool.

Empiric antibiotic therapy �empiric therapy: q An oral fluoroquinolone ( ciprofloxacin 500 mg twice daily, norfloxacin 400 mg twice daily, or levofloxacin 500 mg once daily) for three to five days in the absence of suspected EHEC or fluoroquinolone-resistant campylobacter infection q Azithromycin (500 mg PO once daily for three days) or erythromycin (500 mg PO twice daily for five days) are alternative agents if fluoroquinolone resistance is suspected

Symptomatic therapy �The antimotility agent loperamide (Imodium) may be used in patients with acute diarrhea in whom fever is absent or low grade and the stools are not bloody �The dose of loperamide is two tablets (4 mg) initially, then 2 mg after each unformed stool, not to exceed 16 mg/day for ≤ 2 days. �Diphenoxylate has central opiate effects and may cause cholinergic side effects

Symptomatic therapy �patients should be cautioned that treatment with these agents may mask the amount of fluid lost, since fluid may pool in the intestine. �Thus, fluids should be used aggressively when antimotility agents are employed. �Another potential problem is that both drugs may facilitate the development of the hemolytic-uremic syndrome (HUS) in patients infected with EHEC

Symptomatic therapy �Bismuth subsalicylate (Pepto-Bismol) has also been used for symptomatic treatment of acute diarrhea. � compared with placebo, bismuth subsalicylate is significantly better but compared with loperamide, loperamide is better �A role for bismuth subsalicylate may be in patients with significant fever and dysentery, conditions in which loperamide should be avoided. �Two tablets every 30 minutes for eight doses

Probiotics � Probiotics, including bacteria that assist in recolonizing the intestine with non-pathogenic flora, can also be used as alternative therapy. �Probiotics is useful in treating traveler's diarrhea �diarrhea and acute non-specific diarrhea in children.

Dietary recommendations � The benefit of specific dietary recommendations other than oral hydration has not been wellestablished in controlled trials. � Adequate nutrition during an episode of acute diarrhea is important to facilitate enterocyte renewal � Boiled starches and cereals (eg, potatoes, noodles, rice, wheat, and oat) with salt are indicated in patients with watery diarrhea; � crackers, bananas, soup, and boiled vegetables may also be consumed � Foods with high fat content should also be avoided � In addition, secondary lactose malabsorption is common following infectious enteritis and may last for several weeks to months. Thus, temporary avoidance of lactose-containing foods may be reasonable

Chronic Diarrhea

EPIDEMIOLOGY q Chronic diarrhea affects approximately 5 percent of the population q More than $350, 000 annually from work-loss alone

ETIOLOGY �The principal causes of diarrhea depend upon the socioeconomic status of the population. q 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. q 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).

EVALUATION q 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 q 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.

History 1) A clear understanding of what led the patient to 2) 3) 4) 5) 6) 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 inflammatory bowel disease) Duration of symptoms, nature of onset (sudden or gradual) Travel history Risk factors for HIV infection Weight loss

History 7) Whethere is fecal incontinence (which may be confused with diarrhea) 8) Occurrence of diarrhea during fasting or at night (suggesting a secretory diarrhea) 9) Family history of IBD 10) 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) 11) The presence of systemic symptoms, which may indicate inflammatory bowel disease (such as fevers, joint pains, mouth ulcers, eye redness)

History 12) All medications (including over-the-counter drugs and supplements) 13) A relevant dietary (including possible use of sorbitolcontaining products and use of alcohol) 14) Association of symptoms with specific food ingestion (such as dairy products or potential food allergens) 15) A sexual history (anal intercourse is a risk factor for infectious proctitis and promiscuous sexual activity is a risk factor associated with HIV infection) · 16) A history of recurrent bacterial infections (eg, sinusitis, pneumonia), which may indicate a primary immunoglobulin deficiency.

Physical examination � The physical examination rarely provides a specific diagnosis. However, a number of findings can provide clues These include: 1) findings suggestive of IBD (eg, mouth ulcers, a skin rash, episcleritis, an anal fissure or fistula, 2) the presence of visible or occult blood on digital examination, 3) abdominal masses or abdominal pain

4) evidence of malabsorption (such as wasting, physical signs of anemia, scars indicating prior abdominal surgery) 5) Lymphadenopathy (possibly suggesting HIV infection), 6) Abnormal anal sphincter pressure or reflexes (possibly suggesting fecal incontinence) 7) Palpation of the thyroid and examination for exophthalmos and lid retraction may provide support for a diagnosis of hyperthyroidism.

laboratory evaluation �A large number of tests are available for diagnosing specific causes of diarrhea �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

laboratory evaluation �The minimum laboratory evaluation in most patients should include a complete blood count and differential, erythrocyte sedimentation rate, thyroid function tests, serum electrolytes, total protein and albumin, and stool occult blood � most patients require some form of endoscopic evaluation and mucosal biopsy (either sigmoidoscopy, colonoscopy, or sometimes upper endoscopy), depending upon the clinical setting

�Another useful way to guide specific testing is to attempt to categorize diarrhea as: qwatery diarrhea(secretory or osmotic) qfatty diarrhea qinflammatory diarrhea

Secretory diarrhea q continues despite fasting q is associated with stool volumes >1 liter/day q occurs day and night (in contrast to osmotic diarrhea) �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.

osmotic gap �(290 - 2 ({Na+} + {K+}) �An osmotic gap of >125 m. Osm/kg suggests an osmotic diarrhea �while a gap of <50 m. Osm/kg suggests a secretory diarrhea

�Further testing in patients with secretory diarrhea may include: 1) stool cultures to exclude chronic infection, 2) imaging of the small and large bowel 3) selective testing for secretagogues, such as gastrin or vasoactive intestinal polypeptide

osmotic diarrhea �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 sugarless candies) 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.

� 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 diarrhea 1) 2) 3) 4) 5) 6) Inflammatory diarrhea should be suspected in patients with: clinical features suggesting inflammatory bowel disease, clinical features suggesting C. difficile infection those at risk for opportunistic infections such as tuberculosis those with a travel history. Serum markers of acute inflammation (such as the sedimentation rate and C-reactive protein levels fecal leukocytes and Fecal calprotectin

Inflammatory diarrhea �Diagnosis can usually be established by: �sigmoidoscopy or colonoscopy or �by analysis of stool specimens (ie, culture or testing for C. difficile toxin).

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.

empiric therapy �empiric therapy may be warranted in certain situations: � · When comorbidities limit diagnostic evaluation. � · When a diagnosis is strongly suspected. �Examples include a daycare worker who develops diarrhea after a known outbreak of Giardiasis �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

DEFINITION �Watery Diarrhea: 3 or more liquid or watery stools in 24 h �Dysentery: Presence of blood and/or mucus in stools �Persistent Diarrhea: Diarrhea lasting for 14 days or more

TYPES OF DIARRHEA

COMMON CAUSES OF DIARRHEA- BACTERIA �Vibrio cholera �Shigella �Escherichia coli �Salmonella �Campylobacter jejuni �Yersinia enterocolitica �Staphylococcus �Vibrio parahemolyticus �Clostridium difficile

COMMON CAUSES OF DIARRHEA- VIRUS • Rotavirus • Adenoviruses • Caliciviruses • Astroviruses • Norwalk agents and Norwalk-like viruses

COMMON CAUSES OF DIARRHEA- PARASITE • Entameba histolytica • Giardia lamblia • Cryptosporidium • Isospora

COMMON CAUSES OF DIARRHEAOTHERS • Metabolic disease ØHyperthyroidism ØDiabetes mellitus ØPancreatic insufficiency • Food allergy ØLactose intolerance • Antibiotics • Irritable bowel syndrome

TRANSMISSION �Most of the diarrheal agents are transmitted by the fecal-oral route �Some viruses (such as rotavirus) can be transmitted through air �Nosocommial transmission is possible �Shigella (the bacteria causing dysentery) is mainly transmitted person-to-person

SEASONALITY

PERSON-AT-RISK �Cholera: 2 years and above, uncommon in very young infants �Shigellosis: more common in young children aged below 5 years �Rotavirus diarrhea: more common in young infants and children aged 1 -2 years �E. coli diarrhea: can occur at any age �Amebiasis: more common among adults

TYPES OF VIBRIO CHOLERA �Two major biotypes of Vibrio cholera that cause diarrhea are: ØClassical ØEl. Tor �Two common serotypes of Vibrio cholera that cause diarrhea are: ØInaba ØOgawa

Vibrio cholerae O 139 �Vibrio cholerae in O-group 139 was first isolated in 1992 and by 1993 had been found throughout the Indian subcontinent. This epidemic expansion probably resulted from a single source after a lateral gene transfer (LGT) event that changed the serotype of an epidemic V. cholerae O 1 El Tor strain to O 139. �More information: http: //www. cdc. gov/ncidod/EID/vol 9 no 7/020760. htm

Vibrio vulnificus � The organism Vibrio vulnificus causes wound infections, gastroenteritis or a serious syndrome known as "primary septicema. " � V. vulnificus infections are either transmitted to humans through open wounds in contact with seawater or through consumption of certain improperly cooked or raw shellfish. � This bacterium has been isolated from water, sediment, plankton and shellfish (oysters, clams and crabs) located in the Gulf of Mexico, the Atlantic Coast as far north as Cape Cod and the entire U. S. West Coast. � Cases of illness have also been associated with brackish lakes in New Mexico and Oklahoma. � For more information: http: //hgic. clemson. edu/factsheets/HGIC 3663. htm

TYPES OF SHIGELLA �The major serotypes of Shigella that cause diarrhea are: ØDysenteriae type 1 or Shigella shiga ØShigella flexneri ØShigella sonnei ØShigella boydii

TYPES OF E. COLI �Six major types of Escherichia coli cause diarrhea: Ø Enterotoxigenic E. coli (ETEC) Ø Enteroinvasive E. coli (EIEC) Ø Enteropathogenic E. coli (EPEC) Ø Enterohemorrhagic E. coli (E. coli O 157: H 7) Ø Enteroaggregative E. coli (EAgg. EC) Ø Diffuse adherent E. coli (DAEC)

CLINICAL FEATURE: CHOLERA �Rice-watery stool �Marked dehydration �Projectile vomiting �No fever or abdominal pain �Muscle cramps �Hypovolemic shock �Scanty urine

CLINICAL FEATURE: E. COLI DIARRHEA �Watery stools �Vomiting is common �Dehydration moderate to severe �Fever– often of moderate grade �Mild abdominal pain

CLINICAL FEATURE: ROTAVIRUS DIARRHEA �Insidious onset �Prodromal symptoms, including fever, cough, and vomiting precede diarrhea �Stools are watery or semi-liquid; the color is greenish or yellowish– typically looks like yoghurt mixed in water �Mild to moderate dehydration �Fever– moderate grade

CLINICAL FEATURE: SHIGELLOSIS �Frequent passage of scanty amount of stools, mostly mixed with blood and mucus �Moderate to high grade fever �Severe abdominal cramps �Tenesmus– pain around anus during defecation �Usually no dehydration

CLINICAL FEATURE: AMEBIASIS �Offensive and bulky stools containing mostly mucus and sometimes blood �Lower abdominal cramp �Mild grade fever �No dehydration

LABORATORY DIAGNOSIS �Stool microscopy �Dark field microscopy of stool for cholera �Stool cultures �ELISA for rotavirus �Immunoassays, bioassays or DNA probe tests to identify E. coli strains

ASSESSMENT OF DEHYDRATION

ASSESSMENT OF DEHYDRATION (contd. )

ASSESSMENT OF DEHYDRATION (contd. )

TREATMENT �Rehydration– replace the loss of fluid and electrolytes �Antibiotics– according to the type of pathogens �Start food as soon as possible

COMPOSITION OF ORS

AMOUNT OF SALT LOSS DURING DIARRHEA

ANTIMICROBIAL AGENTS

COMPLICATIONS: WATERY DIARRHEA �Dehydration �Electrolyte imbalances �Tetany �Convulsions �Hypoglycemia �Renal failure

COMPLICATIONS: DYSENTERY �Electrolyte imbalances �Convulsions �Hemolytic uremic syndrome (HUS) �Leukemoid reaction �Toxic megacolon �Protein losing enteropathy �Arthritis �Perforation

VACCINES �An oral cholera vaccine is available, which gives immunity to 50 -60% of those who take the vaccine, and this immunity lasts only a few months. �No vaccines are available against shigellosis �A vaccine against rotavirus diarrhea has been withdrawn recently from the market.

PREVENTION �Safe drinking water and food “Boil it, cook it, peel it, or forget it. " �Hand washing �Proper sanitation