Passage of small amounts of blood in diarrheal stools (hematochezia) may sometimes arise from hemorrhoids or from mucosal tears which are a consequence of the spasm, hypermotility or mechanical irritation at the mucocutaneous junction, irrespective of the underlying cause of the diarrhea. However, persistence of hematochezia is always significant of an infectious or inflammatory cause of diarrhea. In the pediatric patient, bloody diarrhea is most often due to an infectious enteric pathogen. Clues to the identification of the specific agent involved in the disease process may be gleaned from a combination of history taking, physical examination and simple laboratory studies (Table). However, the definitive diagnosis will depend upon the results of bacteriologie or viral cultures, and examinations for pathogenic protozoa, the presence of specific toxins and sometimes on serology titers. The decision to culture the stool specimen can be made after examining the material (preferably the mucopus) for the presence of white blood cells either by methylene blue or Wright's stain, as well as for blood. l If positive, a darkfield or modified Gram's stain examination should be performed to search for organisms resembling Campylobacter and a wet mount preparation examined for amoeba.2 In the presence of diarrhea, stool containing either blood or white blood cells should be sent for bacteriologie culture. Screening the sample for toxin or ova and parasites can be decided upon if the history reveals recent exposure to antibiotics or travel to or from endemic areas of the world.
Endoscopic evaluation of the colon including histologic examination of mucosal biopsy specimens can generally be delayed until laboratory results are available since they add little specific diagnostic information, especially when performed early in the illness. The histologic findings can help, however, in differentiating antibiotic-associated colitis and acute self-limited colitis from idiopathic inflammatory bowel disease.3
Up until 5 to 10 years ago, dysenteric symptoms (abdominal pain, tenesmus, small volume bloody stools) were attributed to shigella, salmonella or amebiasis. Now the list of enteric pathogens responsible for dysenteric disease includes Campylobacter, Yet' sinia, Clostridium difficile, both enteroinvasive and enteropathogenic E. coli, gonococcus, Chlamydia tra' chomatis, and Herpes simplex. Conditions such as necrotizing enterocolitis, allergic colitis, idiopathic inflammatory bowel disease and hemolytic-uremicassociated colitis will be included in the differential diagnosis at least until the results of stool cultures and other screening laboratory tests are available. However, this report will examine in some detail only the bacterial causes of bloody diarrhea.
Shigellosis represents the most common bacterial cause of dysentery-like disease worldwide.4
Shigella belong to the family Enterobacteriaceae and cause intestinal disease in the large bowel. Of the four species recognized (S. dysenteriae, S. flexneri, S. boyan, S. sonnei), most shigellosis in the US is due to S. sonnei (70%) or S. flexneri. S. dysenteriae (Shiga bacillus) is more important in the Orient and in Mexico where it causes severe diarrhea with a mortality rate of over 30%. The disease is most common between 1 and 4 years of age and the incidence is increased during the warmer months of the year.
Bacteriology-The bacilli are gram-negative, nonmotile, non-lactose fermenting, and are capable of producing clinical symptoms after a relatively small inoculum of 101 to 103 organisms. Man appears to be both the main host and reservoir, and although the fecal-oral route is the principal mechanism of spread, ingestion of contaminated food or water has also caused disease.
Pathophysiology-These organisms possess encoded genetic information which apparently stimulates pinocytosis and facilitates their invasion of colonic epithelial cells.4 They multiply in this location releasing a cytotoxin that results in epithelial cell destruction and small ulcerations which may extend to undermine the mucosa, producing a lesion similar to that seen in amebiasis. Access of organisms to the lamina propria incites a marked inflammatory reaction containing both polymorphonuclear and mononuclear cells with prostaglandin release that in turn influences fluid transport across the bowel mucosa. Net secretion occurs in the small bowel while decreased reabsorption is seen in the colon. 5 Animal and human experiments have uncovered a cell wall bound enterotoxin in some strains of S. dysenteriaeA, which may explain cases in which water loss diarrhea, rather than dysentery, dominates the clinical picture. The so called Shiga toxin possesses neuro-, cyto- and enterotoxogenic action and is produced in highest concentrations by S. dysenteriae-1.
BLOODY DIARRHEA OF BACTERIAL ORIGIN
BLOODY DLARRHEA OF BACTERIAL ORIGIN
Clinical Disease-The illness, starting generally after a 36 to 72-hour-incubation period, is ushered in by fever, malaise, abdominal cramps and large volume water loss diarrheal stools. While this picture continues in half the cases, others may over the next 1 to 3 days manifest dysentery symptoms such as crampy lower abdominal pain, urgency and tenesmus, while passing small volume stools containing mucus and blood. Some patients develop an altered level of consciousness or frank seizures suggesting an encephalopathy due to an elaborated neurotoxin rather than to the associated hyperpyrexia. Signs of dehydration, irritability and listlessness with tachycardia, and postural hypotension may be noted. Abdominal distention without peritoneal signs and a patulous anus with congested exposed rectal mucosa are often seen.
The total white count may be normal or markedly elevated while the differential shows a greater number of band forms than of mature segmented neutrophils. Stool examination usually reveals white blood cells and blood. It is important to inoculate promptly the stool specimen onto appropriate culture media. Blood cultures are seldom positive for any shigella other than in S. dysenteriaeA infections. However, bacteremia may occur from other colonic organisms gaining access to the bloodstream as a result of shigella colitis.6 Important negative findings include failure to demonstrate Campylobacter' like organisms by direct microscopy and failure to find trophozoites of amoebae on examination of a freshly obtained stool sample.
Endoscopic and Histologic Features
Caution should be exercised in performing colonoscopy since the risk of perforation is increased in the face of acute dysentery. When performed, the examination reveals mucosal edema, diffuse hyperemia, increased friability, focal hemorrhages, occasional shallow aphthous-like ulcers and mucopurulent exudate. Biopsy of the inflamed mucosa shows edema, a predominantly leukocytic marked inflammatory cell reaction and destruction of the surface epithelial cell layer with microulcerations. Microcrypt abscesses may also be seen but disturbances of general crypt architecture and mucus depletion of grandular epithelium tend to be minimal in shigella infection.
Radiographs-The picture of nonspecific colitis may be seen on barium enema and includes spasm, mucosal edema and superficial ulceration. In extreme examples, the "collar-button" appearance of ulcerations may simulate those of amebiasis.
Treatment-Therapy requires correction of dehydration and of electrolyte imbalance with either oral or intravenous fluids and restitution of vascular volume in severe cases with colloid. Extensive colonic involvement may be associated with protein-losing enteropathy. Treatment with trimethoprim (10mg/kg/d) and sulfamethoxazole (50mg/kg/d) is recommended due to increasing numbers of ampicillin and chloramphenicol-resistant shigetiae. This agent eradicates the organism from the gastrointestinal tract, shortens the duration of illness and reduces the likelihood of subsequent spread. Untreated, the disease is usually self-limited, resolving in 3 to 7 days, though carriage of the organism continues for up to 3 weeks and subsequent disappearance of organisms from the stool correlates with the development of species-specific immunity, albeit incomplete at times. Drugs that decrease intestinal motility and alter physiologic clearing of the organisms are contraindicated. Mortality from shigella dysentery occurs only in malnourished infants and is less than 1% in the US.
Rare complications include toxic megacolon, cholestatic hepatitis and the evolution of the hemolytic uremic syndrome. Patients positive for HLA B-27 seem to be at added risk of developing Reiter's syndrome* following dysenteriae infection.
Salmonella organisms cause several distinct clinical syndromes including enteric fever, gastroenteritis with or without bacteremia, bacteremia with or without intestinal infection, focal infection, and an asymptomatic carrier state. In the US S. enteritidis or a related serotype causes invasive enterocolitis with bloody diarrhea. In contrast to shigellosis, disease from salmonella is more often seen in children under 1 year of age and 40% of all patients are below 5 years of age. By contrast, enteric fever is relatively rare in this country and may manifest diarrhea early in about 10% to 20% of patients but the stools seldom contain blood.
Bacteriology-Salmonellae are a complex group of gram-negative, motile, non-lactose fermenting bacilli belonging to the family Enterobacteriaceae. Infections with S. typhi or with various types of S. paratyphi result directly from fecal-oral human to human contact or indirectly through ingestion of contaminated food or water. Non-typhoidal salmoneüae are endemic to various animal species and human disease results from ingestion of improperly cooked contaminated foodstuffs (meat, eggs, dairy products and homemade ice cream). Large outbreaks have also come from exposure to sewage contaminated water supply or from humanto-human transmission.
Pathophysiology-The invasive properties common to all salmoneüae facilitate their penetration and multiplication in mucosal epithelial cells and the lamina propria. The extent of colonization in distal small bowel and colon appears to depend on the size of the infecting dose, local factors and host immunity. When both terminal ileum and colon are involved, symptoms of diarrhea with mucus, pus and blood are likely. Involvement of the colon or stomach alone has been observed, but pathologic abnormalities restricted to the proximal small intestine are unusual.
Epithelial cell destruction results from the cytotoxin action of the salmonellae, while their invasive properties may lead to an alteration of net water and electrolyte transport, presenting a large fluid load to the colon. Mediators released by the inflammatory cell reaction lead to altered capillary permeability and hemorrhage while local prostaglandin secretion further enhances net secretion. S. enteritidis may contain an enterotoxin that also contributes to fluid secretion.
Clinical Disease-Within 48 hours after exposure to a large inoculum of 106 to 1010 organisms, salmonella gastroenteritis develops with nausea with or without vomiting, fever, malaise and abdominal cramps. The diarrhea which follows may consist of loose stools of moderate volume or manifest more features of dysentery, with frequent small volume stools accompanied by urgency, tenesmus and lower abdominal pain. Globs of mucus and blood are usually apparent in freshly passed stools. Extreme vomiting and profuse diarrhea commencing within the first 24 hours may rapidly lead to dehydration, shock and cardiovascular collapse, especially in neonates and infants, in whom bacteremia is also likely. Occasionally the clinical presentation includes vomiting, abdominal distention, rebound tenderness and decreased bowel sounds and mimics the clinical features of acute appendicitis, toxic megacolon, or of acute pancreatitis.
Laboratory Features-In salmonella gastroenteritis the white blood count is low, normal, or moderately elevated with a left shift, in contrast to the leukopenia with lymphocytosis of enteric fever. The stools in 50% of patients contain obvious or occult blood and a moderate number of white blood cells. Several stool cultures may be necessary for bacteriologie confirmation and blood cultures should be obtained in all febrile children less than 1 year of age.
Endoscopic and Histologic Features-Colonoscopy reveals edema and hyperemia in milder cases with colonic involvement, with punctate hemorrhages, increased friability and small ulcerations covered by mucopus in more severe examples. Biopsies consistent with infective colitis exhibit mucosal edema, polymorphonuclear cells in the mucosal inflammation, minimal distortion of crypt architecture and little depletion of goblet cell mucus. More severe cases may show epithelial disruption more consistent with Crohn's colitis than with the picture of acute ulcerative colitis. 10 Small bowel changes include ulceration, shortened intestinal villi and a mononuclear cell infiltrate of the lamina propria.
Radiographs-Abdominal distention and rebound tenderness dictate radiographic studies for signs of perforation or of toxic dilation of the colon. A lesion suggesting ulcerative colitis has been noted in rare barium enema studies.
Differential Diagnosis-Other known causes for dysentery such as Shigelh, Campylobacter, Yersinia and Entamoeba histolytica need to be considered. The acute onset of inflammatory bowel disease cannot be ruled out, especially in school age or adolescent patients, even after clinical, endoscopic and histologic assessment. When localized lower abdominal pain is present, acute appendicitis needs also to be included in one's differential diagnosis.
Treatment-Prompt correction of dehydration and electrolyte imbalance with either an oral glucose electrolyte solution or intravenous fluids is indicated. Antibiotics alter neither the duration of illness nor time to recovery from gastroenteritis, and their usage prolongs the intestinal carriage of salmonella and increases both the bactériologie and symptomatic relapse rate.11 Antibiotics are recommended, however, in the following patients: 1) those suspected of having bacteremia (increased toxicity, fever over 102°; 2) those at increased risk for bacteremia (neonates and children under 1 year); 3) those with lymphoproliferative diseases; 4) those with hemolytic anemias or hemoglobinopathies; 5) those on immunosuppressive therapy; and 6) those with congenital heart disease or valvular cardiac disorders.
Intravenous chloramphenicol (100 mg/kg/d in 4 divided doses), combined with trimethoprim (lo mg/ kg/d) -sulfamethoxazole (50 mg/kg/d) should be continued for at least 14 days in severely ill patients. Highdose steroids have been recommended for extremely ill patients. Indomethicin or other prostaglandin inhibitors may be employed to reduce gastrointestinal fluid and electrolyte losses. Two consecutive negative stool cultures taken 24 hours apart are regarded as bacteriologie cures. Untreated cases may continue fecal shedding of salmonella for up to 2 months.
Clinical Course-Spontaneous clinical and pathologic improvement usually occurs in 5 to 14 days. Persistence of dysentery-like symptoms may indicate underlying inflammatory bowel disease.
Members of the genus Campylobacter (previously classified as a Vibrio) have long been known to be responsible for abortion in cattle and sheep. One species, C. jejuni has emerged as a leading cause of human enteritis in the past decade. In several studies, it has been recovered from 3% to 14% of diarrheal stools, an isolating rate equal to or greater than that of shigella or salmonella.
Bacteriology-C. jejuni is a motile, gram-negative, curved or spiral bacillus with fastidious growth requirements. Household pets, including puppies and kittens, may serve as reservoirs for infections acquired by toddlers and young children. Acquisition is usually via ingestion of contaminated food or water or indirectly from handling infected household pets.
Pathophysiology-The illness starts 2 to 7 days after exposure. Ingested organisms survive gastric acid peptic digestion and thrive in the microaerophilic environment of the small intestine. Small bowel and colon can both be involved with penetration of the lamina propria either directly or after cytolytic exotoxin-mediated epithelial cell destruction but the exact mechanism by which C. jejuni causes disease is still unclear.12 The bacterial cell wall also contains endotoxin properties.13 Certain strains of C. jejuni may produce a secretory diarrhea-like illness rather than the more typical inflammatory colitis. Bacteremia is rare.
Clinical Disease-Though the frequency decreases after age 7 to 8 years, all age children, including neonates, seem to be vulnerable, primarily during the summer months. Onset is abrupt with fever, periumbilical colicky pain, and diarrhea of loose, watery copious stools which become grossly bloody (flecks, streaks, drops) in two-thirds of the cases within 2 to 4 days. Vomiting is reported in one-third of affected individuals. Urgency, lower abdominal pain, and stool incontinence are particularly impressive in patients with colonic involvement. Surprisingly, dehydration is seldom of clinical significance. Hemorrhagic necrosis of the jejunum is a severe manifestation heralded by signs of peritoneal irritation. Seizures and reactive arthritis have been noted in a few patients.
Laboratory Features-The white blood count may be normal, any elevation being accompanied by a left shift. If the mucopus portion of a freshly obtained stool sample is positive for blood (hematest) and WBCs (methylene blue stain), and darkfield microscopy of the sample shows the darting motility pattern typical of Campylobacter, the presumptive diagnosis will prove positive from cultures plated on special culture media.
Endoscopic and Histologic Features-The colonoscopic appearance is often a diffuse nonspecific colitis with an erythematous, edematous and friable epithelium, coated with mucopus mixed with a bloody exudate. Both patchy, focal and segmental mucosal ulcerations of the colon similar to those seen in Crohn's disease have been observed. 14 Colonic biopsies also show a variable degree of microcrypt abscesses and goblet cell depletion simitar to those of ulcerative colitis, but without generalized epithelial ulcerations.
Radiography-Barium enema may show features of pancolitis, erroneously suggesting chronic ulcerative colitis.
Differential Diagnosis-Early on, C. jejuni infection cannot easily be differentiated from disease due to shigella, salmonella, amebiasis, chronic ulcerative colitis or Crohn's colitis. Diagnosis rests on positive stool culture with dismissal of the other considerations by the patient's subsequent clinical course.
Treatment-Most cases of C. jejuni enterocolitis resolve spontaneously within 7 to 14 days, while 20% may manifest continuous or relapsing disease. Although the efficacy of antibiotics remains controversial, erythromycin stéarate or ethyl-succinate, 30 to 50 mg/kg/d orally, is utilized to eliminate fecal excretion of this organism within 48 to 72 hours, in the face of severe toxicity, copious bloody diarrhea, severe abdominal pain or a prolonged course.
Clinical Course-The profuse diarrhea, hematochezia and abdominal pain generally resolve within 2 to 3 days and a normal bowel pattern returns gradually over 1 to 2 weeks, with persistence or relapses with intermittent discomfort or loose stools for more than 3 to 4 weeks occurring in less than 10% of patients. Persistent fever, colicky pain, and an abdominal mass suggest an inflammatory pseudotumor within an infected mesenteric lymph node. Former spontaneous "cures" of chronic ulcerative colitis may indeed have been undiagnosed cases of protracted Campylobacter infection.
The hemolytic uremic syndrome has recently been associated with Campylobacter colitis.16
Most early reports implicating Yersinia in gastrointestinal disease originated from Scandinavia. The organism was responsible for 2.8% of gastroenteritides among 6,364 Canadian children.17 The prevalence rate in random stool samples in US studies has been placed at 0. 4% to 0. 7%, with evidence over a 6-month period in Colorado indicating Yersinia to be the pathogen in 11 of 395 cultures (2.9%) obtained from individuals with abdominal pain and diarrhea.
Bacteriology-The genus Yersinia belongs to the family Enterobacteriaceae. Isolation of these gramnegative, aerobic, motile, nonlactose-fermenting cocco-bacilli is improved by cold enrichment techniques. Y enterocolitica O-serotypes 3,8,9, and Y. pseudotuberculosis ss. pseudotuberculosis serotype 1-A most commonly cause human disease following ingestion of contaminated food or water, and less commonly by person-to-person spread.18 Although usually recovered from stool samples, positive cultures have also been reported from blood, CSF, throat, eye discharge, urine and mesenteric lymph nodes obtained intraoperatively. Infection results in development of humoral antibody to the specific serotype (lipopolysaccharide hemagglutination).
Pathophysiology-The organism produces enterotoxin, similar to E. coli, which stimulates adenylcyclase and cyclic AMP, causing secretion of electrolytes and fluid into the bowel lumen. Some strains of Y. enterocolitica also have invasive properties. Surface ulcerations and necrosis within Peyer's patches are believed to result from a cytotoxin which also causes exudative diarrhea with white blood cells and hematochezia. Failure of gastrointestinal tract containment results in septicemia or of localized distant infections involving joints, heart, kidney, liver, skin (erythema nodosum) and CNS. Bacterial antigen antibody complexes may explain some of these extrabowel manifestations. In vitro bacterial multiplication is enhanced by iron enriched media and may relate to a susceptibility to Y. enterocolitica infection among patients with iron "overload" conditions, ie, thalassemia, aplastic anemia, hemachromatosis.19
Clinical Disease-The most common clinical syndrome caused by Y. enterocolitica includes fever, crampy abdominal pain, vomiting and diarrhea with gross or occult blood in the stool in over 25% of cases.17 A majority of cases in infants and young children resolves spontaneously in 3 to 7 days but some continue with more chronic colicky abdominal cramps, diarrhea and hypoproteinemia. Rarely, children also develop extra intestinal manifestations such as septic arthritis, erythema nodosum, meningoencephalitis, myocarditis, nephritis, and hepatitis. A septicemic form of the disease may be seen in the immune compromised host.
An acute ileitis syndrome characterized by low grade fever, abdominal pain, with or without dianhea, and a moderate leukocytosis mimics appendicitis or acute mesenteric lymphadenitis so closely that the dilemma may only be resolved when surgery reveals the distal ileal inflammation, enlarged regional lymph nodes and normal appendix.20 These findings may suggest Crohn's disease but culture of the involved lymph nodes is positive for Yersinia in up to 20% of cases. Peyer's patches involvement may lead to perforation of the ileum from abscess formation and to ilecolic intussusception from hypertrophy.21
Laboratory Features-Leukocytosis, which is common, may help with differentiation from chronic S. typhi disease. Stools are green, loose, not exceptionally malodorous, usually with hematochezia, and methylene blue stain reveals scant numbers of leukocytes. Serologic testing is difficult and cumbersome due to cross-reacting antigens of other bacteria. The hemagglutination titer to specific serotypes persists for 5 to 6 months after acute infection.
Endoscopic and Histologic Features-When involved, the colon shows mucosal edema, scattered aphthoid ulcerations, increased friability, and in severe cases pseudomembrane formation has been observed. Biopsy demonstrates acute inflammation with a predominance of mononuclear cells over polymorphonuclear leukocytes. Punctate or linear ulcers are usually found over lymphoid aggregates. Neither giant cells nor granulomata are seen.
Radiography-Plain films may show nonspecific ileus. The barium enema is usually free of mucosal abnormalities but the cecum is frequently deformed, possibly due to spasm. On small bowel study the distal 20 to 25 cm of ileum is typically involved. Mucosal edema, prominent Peyer's patches, coarse nodularity and linear ulcerations are usually seen, sometimes in association with adherent adjacent loops around this portion of the small bowel, attributed to local fibrinous serositis and peritonitis.
Differential Diagnosis-In patients with gastrointestinal symptoms, dysentery due to shigetia, salmonella, Campylobacter, or amebiasis must be considered. If fever and abdominal pain predominate, acute appendicitis, periappendiceal abscess, Crohn's ileitis, amebiasis and mesenteric lymphadenitis are the difficult differentials.
Treatment-Since most cases resolve spontaneously within 2 weeks, few patients require anything beyond general supportive measures. Systemic antibiotics are indicated for septicemia. Treatment decisions involve epidemiologic considerations since fecal shedding of the organism may continue well beyond cessation of diarrhea and patients remain potential vectors for spread, especially to toddlers and young children in day care or nursery environments. The organism is susceptible to the aminoglycosides, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole.
Clinical Course-Gastroenteritis is generally self limited to 7 days or less but the endoscopic and radiographic abnormalities may persist for 2 to 3 months, occasionally for up to 6 months.
Since 1978 C. difficile and its elaborated cytotoxin are identified as responsible for a diarrhea-associated illness commencing during or after exposure to most antibiotics, especially ampicillin, clindamycin and the cephalosporins. 22 The organism can be recovered from 30% to 50% of asymptomatic neonates, some of whom also have toxin in their stools. The 3% of individuals who carry C. difficile beyond 1 year of age remain at risk of developing antibiotic-associated colitis.
Bacteriology-Clostridia are ubiquitious grampositive anaerobic rods. Proliferation of the organism and toxin production are promoted by alteration of the normal colonic flora during antibiotic treatment. Local environmental spread is also facilitated by ingestion of spores produced by the organism.23
Pathophysiology-Carriers who are subjected to antibiotic therapy develop accelerated colonic growth of C. difficile and toxin is elaborated following lysis of the increased numbers of organisms. Two toxins have been identified. Toxin A exhibits in vivo gastrointestinal potency in animals with less cytopathic in vitro activity, while toxin B shows opposite characteristics.24
Clinical Disease-The clinical illness varies from mild diarrhea to a more severe process with fever, crampy abdominal pain, dehydration, hypoproteinemia, abdominal distention, with progression on rare occasions to toxic megacolon and colonic perforation. Although the bloody diarrhea usually commences during a period of antibiotic therapy, it may begin as late as 1 to 2 weeks after discontinuation of administration in one-third of cases. C. difficile may also occasionally cause chronic diarrhea and failure to thrive without the picture of colitis.25
Laboratory Features-The white blood count is normal to somewhat elevated, sedimentation rate is characteristically normal, and stools usually contain white blood cells and blood. Since direct culture for C. difficile is difficult, stool samples are tested for the elaborated toxin and results are likely to be positive in up to 95% of patients with pseudomembranous colitis. Only 15% to 25% of patients without pseudomembrane formation show a positive toxin assay.
Endoscopic and Histologic Features-The pathologic lesion of C. difficile is within reach of the standard 22 cm sigmoidoscope in over 75% of patients and is demonstrated in up to 90% if 50 to 60 cm of distal colon is examined. Mild cases include edema and patchy erythema without plaque formation. More advanced processes may suggest ulcerative colitis with edema, hemorrhage and increased friability. Those with pseudomembranous colitis show firmly adherent, whitish-yellow plaque like lesions, which may either be confluent or in patches separated by normal appearing mucosa which may have the histologic picture of nonspecific acute inflammation. The plaques consist of a fibrin exudate containing mucus, polymorphonuclear cells, and degenerating epithelial cells with distended mucous glands surrounded by an acute inflammatory reaction in the underlying mucosa. Crypt abscesses are rare.
Radiography-The nodular mucosa may resemble pseudopolyps when seen on barium enema. The mucosal irregularities simulate a "dirty colon" or improperly cleansed bowel with decreased haustral markings and thickened folds. Submucosal edema produces a "thumb-printing" effect and toxic megacolon may also be observed. On rare occasions perforation with air under the diaphragms has been reported.
Differential Diagnosis-All infections and inflammatory causes of dysentery previously discussed need to be considered unless pseudomembranous changes are noted. The history of recent (up to 6 weeks) antibiotic usage helps to focus in on the correct diagnosis.
Treatment-Most patients respond simply to discontinuation of the antibiotic but more severe cases may require intravenous fluids, including colloids, for the associated protein-losing enteropathy. Vancomycin given orally in the dose of 10 to 40 mg/kg/d for 7 to 10 days is said to be effective in 95% of cases of C. difficile caused disease, though the subsequent relapse rate may approach 20%. 26 Metronidazole (Flagyl) in a dose of 15 to 40 mg/kg/d for 7 days and oral bacitracin at 1 ,000 to 1 ,500 u/kg/d in divided doses have also been effective with a relapse rate that is similar to that for vancomycin. Cholestyramine binds the toxin but does not eradicate the organism and can also be used. Opiate-like agents as well as anticholinergics should be avoided and surgery is rarely necessary in treating this disease.
Clinical Course-Although the diarrhea resolves spontaneously in the vast majority of patients, the subsequent relapse rate of 10% to 20% and fatality rates among debilitated children and the elderly of up to 25% to 30% are causes for concern. Chronic relapsing disease, probably from reinfection via ingestion of C. difficile spores which are present in the local environment and spread to family members or to other hospitalized patients on antibiotics are of further concern. Finally, intractable proctitis due to C. difficile has been reported, and it may eventually require surgical resection for cure.
Escherichia coli have been shown to produce clinical disease in humans by several distinct mechanisms27:
A. Enterotoxigenic: E. coli strains (ETEC) capable of releasing a plasmid-coated enterotoxin, be it the heat labile (LT) or heat stable (ST) variety or both, cause a diarrhea illness that is secretory (cholera-like) in nature. Though the patients manifest crampy abdominal pain, urgency, nausea and low grade fever, the stools are devoid of blood and polymorphonuclear leukocytes.
B. Enteroinvasive: Serotypes of E. coli which possess enteroinvasive (EIEC), rather than enterotoxigenic properties are responsible for a dysentery-like syndrome. ElEC invade mucosal epithelial cells, are cytotoxic and lyse cell membranes. They are also found in the lamina propria, especially in the distal small bowel and proximal colon, where, either by their own toxin production or from that released by the host's inflammatory cell reaction, they cause an illness characterized by low grade fever, crampy abdominal pain, and diarrhea, frequently indistinguishable from that caused by shigella or salmonella. Stools contain microscopic or gross blood, mucus, and polymorphonuclear leukocytes.
Since the organism does not invade beyond the lamina propria, perforation of the bowel does not occur. Systemic antibiotics preferred for invasive disease (ampicillin, gentamycin, aminoglycosides) are seldom indicated in this self-limited entity which is usually mild and ends in 2 to 5 days. Bacterial confirmation of ElEC requires a combination of serotyping and testing for invasiveness, procedures not routinely available in most hospital laboratories, and requires investigations from the local State Health Department of from the Centers for Disease Control in Atlanta, Georgia.
C. Enteropathogenic: Enteropathogenic E. coli (EPEC) usually colonize the small bowel producing severe diarrhea in newborns and young children. With rare exception these serotypes of E. coli are lacking in LT and ST activity and are Sereny test negative.
Reports of outbreaks of hemorrhagic colitis associated with a certain strain of EPEC (0124:B17) have appeared sporadically from japan and eastern Europe. A clustering of cases first appeared in the US in 1971 when imported French cheese was found contaminated by this organism.28 Surprisingly, organisms isolated from the infected patients and cheese specimens revealed a positive Sereny test for invasiveness. The illness commenced from 2 to 24 hours (mean 18 hours) after ingestion and was characterized by moderate fever (103° or greater), nausea, cramps and watery diarrhea, the latter changing to grossly bloody stools. The lesion seen on sigmoidoscopy was that of hyperemia with or without superficial ulcerations. Spontaneous improvement within 48 hours was the rule.
Another recent outbreak of hemorrhagic colitis was attributed to ingestion of hamburger meat contaminated with a rare enteropathogenic serotype of E. coU (0157:H7).29 Infected patients became ill within 3 to 4 days after exposure and all experienced severe crampy abdominal pain, little or no fever, and watery diarrhea that rapidly changed to grossly bloody stools within the next 24 hours. Many patients required hospitalization for intravenous fluid rehydration. Laboratory data showed a leukocytosis with a left shift. Sigmoidoscopy showed the mucosa to be hyperemic in a few patients. Biopsies revealed little or no inflammatory reaction although diffuse mucosal hemorrhage and superficial erosions were noted. The disease ran a benign course of gradual improvement over 4 to 5 days without complications or sequelae.
Of particular interest has been a recent demonstration that certain strains of EPEC, especially the 026 group but also including 0157:H7, have cytotoxin activity against Vero cells grown in tissue culture. This cytotoxin (VT) closely resembles the "Shiga-toxin" elaborated by Shigella dysenteriae-l and when present is thought to confer enteroinvasive properties to these strains of E. coli. The association of VT and E. coli (026, 0113, Olli, 0157) in the stool of some patients with hemolytic uremic syndrome colitis and shigella has been reported.30
VENEREALLY ACQUIRED BACTERIAL AGENTS
Infections of the distal bowel causing bloody diarrhea can, even in the pediatric age group, be due to venereally acquired organisms. Such a possibility should be included in one's differential diagnosis if the patient admits to being a willing participant in homosexual practices or if sexual abuse is probable in a particular child. Not only have the traditional organisms associated with venereal disease been implicated as causative in cases of bloody diarrhea (N. gonorrhea, C. trachomatis, H. simplex) but rectal infections due to sexually acquired shigella, campyhbacter, giardia and amebiasis have also been identified.
1. Pickering LK, DuPont HL, Otarte J1 et ali Fecal leukocytes in enteric infection!,. Am J Clin Pathol 1977; 68:562-565.
2. Paisley JW1 Mirrett S, Lauer BA, et al: Dark-field microscopy of human feces for presumptive diagnosis of Campylobacter fetus suhsp. jejuni enteritis. J Clin Microbial 1982:15:61-63.
3. Surawicz CM , Belie L: Rectal biopsy helps to distinguish acute self-limited colitis from idiopathic inflammatory bowel disease. Gastroenterology 1984; 86: 104- 113.
4. Levine MM: Bacillary dysentery. Med Clin North Am 1982; 66:623-636.
5. Keusch GT, Jacewicz M: The pathogenesis of shigella diarrhea. Vl. Toxin and antitoxin in Shigella /lexneri and Shigella sonner infections in humans. J lnfec Dis 1977; 135:552556.
6. Duncan B, Fulginiti VA, Sieber OF, et al: Shigella sepsis. Am ) Du Child 1981; 135:151-154.
7. Chang MJ, Dunkle LM, Reken DV, et al; Trimethoprim-siilfamethoxatole compared to ampkillin in the treatment of shigellosis. Pediatrics 1977; 59:726-729.
8. Ryder R1 Merson M, Pollard R, et al: Salmonellosis In the United States. ) lnfec Dis 1976;133:483-486.
9. H yams JS, Durbin WA, Grand RJ, et al: Salmonella bacteremia in the first year of life. Pediatr 1980; 96:57-59.
10. Day DW, Mandai BK, Morson BC: The rectal biopsy appearances in Salmonella Colitis. Hutopaihoiogy 1978; 2:117-131.
11. Nelson JD, Kusmiesz H, Jackson LH, et al: Treatment of salmonella gastroenteritis with ampkillin, amoxicillin or placebo. ftdiamcs 1980; 63:1 125-1 130.
12. Blaser MJ. Relier LB: Campylobacter enteritis. N Engl J Med 1981; 305:1444-1452.
13. Johnson WM, Lior H: Toxins produced by Campylobacter jejuni and camfniuhocier coli. Lancet 1984; 1:229-230.
14. Loss RW Jr, Mangia JC, Pereira M: Campylobacter colitis presenting as inflammatory bowel disease with segmental colonic ulcerations. Gastroenterology 1 980; 79: 1 38-140.
15. Blaser MJ, Berkowitz ID, LaForce FM, et al: Campylobacter enteritis: Clinical and epidemiologic features. Ann Intern Med 1979; 91:179-185.
16. Chamovitz BN, Hartstein Al, Alexander SR, et al: Campylobacter jejuni-associated hemolytic -uremic syndrome in a mother and daughter. Ptdkancs 1983; 71:255-256.
17. Marks MI, fai CH, Lafleur L, et al: Yersinia eruerotoaaca gastroenteritis: A prospective study of clinical bacteriologie, and epidemiologic features. J IVaW 1980; 96:26-51.
18. Snyder JD, Christenson E, Feldman RA: Human Yersinia enterocolitica infections in Wisconsin. AmJ Med 1982; 72:768-774.
19. Butzler JP, Alexander M, Segers A, et al: Enteritis, abscess and septicemia due to Yersinia enterocoltOca in a child with thalassemia. ) Pediatr 1978; 93:619-621.
20. Weber J, Finlayson NB, Mark JBD. Mesenteric lymphadenitis and terminal ileitis due to Yersmiapseudoti4berculojis. N Engl J Med 1970; 283:172-174.
21. Burchfield DJ, Rawlings D, Hamrick HJ: Intussusception associated with Yersinia enterocoiiuca gastroenteritis. AmJDuCiHiId 1983; 137:803-804.
22. Bartlett JG, Chang T, Gurwith M, et al: Antibiotic -associated pseudomembranous colitis due to toxin-producing Clostridia. N Engl J Med 1978;298:531-534.
23. Kim K, Dufont HL, Pickering LK: Outbreaks of diarrhea associated with Clostridium difficile and its toxin in day-care centers: Evidence of person-to-person spread. J Pediatr 1983;102:376-382.
24. Taylor NS, Thome GM. Bartlett JG: Comparison of two toxins produced by Clostridium difficult. lnfec Immun 1982; 34:1036-1043.
25. Schwarz RP, Ulshen MH: Pseudomembranous colitis presenting as mild, chronic diarrhea in childhood. ) Pediatr Gastroenterol Nutr 1983; 2:570-573.
26. George WL, Rolfe FD, Finegold SM: Treatment and prevention of antimicrobial agent-induced colitis and diarrhea. Gastroenterology 1980; 79:366-372.
27. Ruwe B: The role of Escherichia coli in gastroenteritis. CIm Gastroenterol 1979; 8:625-644.
28. Marier R, Wells JG, Swanson RC, et al: An outbreak of enteropathogenic Escherichia coli foodborne disease traced to imported French cheese. Lancet 1973; ii: 1 376- 1 378.
29. Riley LW, Remis RS, Helgcrson SD, et al: Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engt J Med 1983; 308:681-685.
30. Karmali MA, Petric M, Steele BT, et al: Sporadic cases of hacmolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia culi in stools. Lancet 1983; i:619-620.
BLOODY DIARRHEA OF BACTERIAL ORIGIN
BLOODY DLARRHEA OF BACTERIAL ORIGIN